13 research outputs found
Short-term low-protein diet during pregnancy alters islet area and protein content of phosphatidylinositol 3-kinase pathway in rats
Inhibition of Ca2+ signaling and glucagon secretion in mouse pancreatic alpha-cells by extracellular ATP and purinergic receptors
Glucagon secreted from pancreatic alpha-cells plays a critical role in glycemia, mainly by hepatic glucose mobilization. In diabetic patients, an impaired control of glucagon release can worsen glucose homeostasis. Despite its importance, the mechanisms that regulate its secretion are still poorly understood. Since alpha-cells are particularly sensitive to neural and paracrine factors, in this report we studied the role of purinergic receptors and extracellular ATP, which can be released from nerve terminals and beta-cell secretory granules. Using immunocytochemistry, we identified in alpha-cells the P2 receptor subtype P2Y(1), as well as the P1 receptors A(1) and A(2A). In contrast, only P2Y(1) and A(1) receptors were localized in beta-cells. To analyze the role of purinergic receptors in alpha-cell function, we studied their participation in Ca2+ signaling. At low glucose concentrations, mouse alpha-cells exhibited the characteristic oscillatory Ca2+ signals that lead to secretion. Application of ATP (1-10 mu M) abolished these oscillations or reduced their frequency in alpha-cells within intact islets and isolated in culture. ATP gamma S, a nonhydrolyzable ATP derivative, indicated that the ATP effect was mainly direct rather than through ATP-hydrolytic products. Additionally, adenosine (1-10 mu M) was also found to reduce Ca2+ signals. ATP-mediated inhibition of Ca2+ signaling was accompanied by a decrease in glucagon release from intact islets in contrast to the adenosine effect. Using pharmacological agonists, we found that only P2Y(1) and A(2A) were likely involved in the inhibitory effect on Ca2+ signaling. All these findings indicate that extracellular ATP and purinergic stimulation are effective regulators of the alpha-cell function.o TEXTO COMPLETO DESTE ARTIGO, ESTARÁ DISPONÍVEL À PARTIR DE AGOSTO DE 2015.2945E952E96
Characterization of the peroxidase system at low H2O2 concentrations in isolated neonatal rat islets
B cell destruction during the onset of diabetes mellitus is associated with oxidative stress. In this work, we attempted to further trace the fate of H2O2 inside the pancreatic islets and determine whether it is mediated by enzymatic (peroxidase) activity or by chemical reaction with thiols from any protein chain. Our results suggest that the islet cells have a very similar peroxidase activity at the hydrophilic (cytoplasm) and hydrophobic compartments (organelles and nucleus), independent of the catalase content of the samples. This activity is composed of sacrificial thiols and by proteins with Fe3+/Mn3+ ions at non-heme catalytic sites. The capacity of the hydrophobic fraction to scavenge O-2(-) was increased in the presence of high concentrations of NADP and RS and was highly dependent on RSH. On the contrary, the hydrophilic fraction exhibited a low RSH-dependent activity where the O-2(-) scavenging is related to metal Cu2+/Fe3+/Mn3+ ions attached to the protein molecules. (C) 2004 Elsevier B.V. All rights reserved.1690215916
Impaired insulin secretion and decreased expression of the nutritionally responsive ribosomal kinase protein S6K-1 in pancreatic islets from malnourished rats
Low protein diet has been shown to affect the levels and activities of several enzymes from pancreatic islets. To further extend the knowledge on how malnutrition affects insulin secretion pathway, we investigated in this work the insulin release induced by glucose or leucine, an insulin secretagogue, and the expression of insulin receptor (IR), insulin receptor substrate 1 (IRS1), phosphatidylinositol 3-kinase (PI3K), and p70S6K1 (S6K-1) proteins from pancreatic islets of rats fed a normal (17%; NP) or a low (6%; LP) protein diet for 8 weeks. Isolated islets were incubated for I h in Krebs-bicarbonate solution containing 16.7 mmol/L of glucose, or 2.8 mmol/L of glucose in the presence or absence of 20 mmol/L of leucine. Glucose- and leucine-induced insulin secretions were higher in NP than in LP islets. Western blotting analysis showed an increase in the expression of IR and PI3K protein levels whereas IRS1 and S6K-1 protein expression were lower in LP compared to NP islets. In addition, S6K-1 mRNA expression was also reduced in islets from LP rats. Our data indicate that a low protein diet modulates the levels of several proteins involved in the insulin secretion pathway. Particularly, the decrease in S6K- I expression might be an important factor affecting either glucose- or leucine-induced insulin secretion. (c) 2008 Published by Elsevier Inc.824192154254
Impaired Insulin Secretion And Decreased Expression Of The Nutritionally Responsive Ribosomal Kinase Protein S6k-1 In Pancreatic Islets From Malnourished Rats
Low protein diet has been shown to affect the levels and activities of several enzymes from pancreatic islets. To further extend the knowledge on how malnutrition affects insulin secretion pathway, we investigated in this work the insulin release induced by glucose or leucine, an insulin secretagogue, and the expression of insulin receptor (IR), insulin receptor substrate 1 (IRS1), phosphatidylinositol 3-kinase (PI3K), and p70S6K1 (S6K-1) proteins from pancreatic islets of rats fed a normal (17%; NP) or a low (6%; LP) protein diet for 8 weeks. Isolated islets were incubated for 1 h in Krebs-bicarbonate solution containing 16.7 mmol/L of glucose, or 2.8 mmol/L of glucose in the presence or absence of 20 mmol/L of leucine. Glucose- and leucine-induced insulin secretions were higher in NP than in LP islets. Western blotting analysis showed an increase in the expression of IR and PI3K protein levels whereas IRS1 and S6K-1 protein expression were lower in LP compared to NP islets. In addition, S6K-1 mRNA expression was also reduced in islets from LP rats. Our data indicate that a low protein diet modulates the levels of several proteins involved in the insulin secretion pathway. Particularly, the decrease in S6K-1 expression might be an important factor affecting either glucose- or leucine-induced insulin secretion. © 2008.829-10542548Amaral, M.E., Ueno, M., Carvalheira, J.B., Carneiro, E.M., Velloso, L.A., Saad, M.J., Boschero, A.C., Prolactin-signal transduction in neonatal rat pancreatic islets and interaction with the insulin-signaling pathway (2003) Hormone and Metabolic Research, 35 (5), pp. 282-289Araujo, E.P., Amaral, M.E., Souza, C.T., Bordin, S., Ferreira, F., Saad, M.J., Boschero, A.C., Velloso, L.A., Blockade of IRS1 in isolated rat pancreatic islets improves glucose-induced insulin secretion (2002) FEBS Letters, 531 (3), pp. 437-442Araujo, E.P., Amaral, M.E., Filiputti, E., De Souza, C.T., Laurito, T.L., Augusto, V.D., Saad, M.J., Carneiro, E.M., Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2 (2004) Journal of Endocrinology, 181 (1), pp. 25-38Aspinwall, C.A., Qian, W.J., Roper, M.G., Kulkarni, R.N., Kahn, C.R., Kennedy, R.T., Roles of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and release of intracellular Ca2+ stores in insulin-stimulated insulin secretion in beta-cells (2000) Journal of Biological Chemistry, 275 (29), pp. 22331-22338Barbera, A., Gudayol, M., Eto, K., Corominola, H., Maechler, P., Miro, O., Cardellach, F., Gomis, R., A high carbohydrate diet does not induce hyperglycaemia in a mitochondrial glycerol-3-phosphate dehydrogenase-deficient mouse (2003) Diabetologia, 46 (10), pp. 1394-1401Bordin, S., Boschero, A.C., Carneiro, E.M., Atwater, I., Ionic mechanisms involved in the regulation of insulin secretion by muscarinic agonists (1995) Journal of Membrane Biology, 148 (2), pp. 177-184Brand, S.J., Morgan, R.G., The influence of starvation on intestinal cholecystokinin-like activity and pancreatic growth (1981) The Journal of physiology, 321, pp. 469-482Bruhat, A., Jousse, C., Fafournoux, P., Amino acid limitation regulates gene expression (1999) Proceedings of the Nutrition Society, 58 (3), pp. 625-632Cetin, I., Amino acid interconversions in the fetal-placental unit: the animal model and human studies in vivo (2001) Pediatric Research, 49 (2), pp. 148-154Chehter, E.Z., Duarte, M.I., Takakura, C.F., Longo, M.A., Laudanna, A.A., Ultrastructural study of the pancreas in AIDS (2003) Pancreas, 26 (2), pp. 153-159Cherif, H., Reusens, B., Dahri, S., Remacle, C., A protein-restricted diet during pregnancy alters in vitro insulin secretion from islets of fetal Wistar rats (2001) Journal of Nutrition, 131 (5), pp. 1555-1559Claeyssens, S., Lavoinne, A., Vaillant, C., Rakotomanga, J.A., Bois-Joyeux, B., Peret, J., Metabolic changes during early starvation in rats fed a low-protein diet in the postweaning growth period (1992) Metabolism, 41 (7), pp. 722-727Conus, N.M., Hemmings, B.A., Pearson, R.B., Differential regulation by calcium reveals distinct signaling requirements for the activation of Akt and p70S6k (1998) Journal of Biological Chemistry, 273 (8), pp. 4776-4782Delghingaro-Augusto, V., Ferreira, F., Bordin, S., do Amaral, M.E., Toyama, M.H., Boschero, A.C., Carneiro, E.M., A low protein diet alters gene expression in rat pancreatic islets (2004) Journal of Nutrition, 134 (2), pp. 321-327Dickson, L.M., Lingohr, M.K., McCuaig, J., Hugl, S.R., Snow, L., Kahn, B.B., Myers Jr., M.G., Rhodes, C.J., Differential activation of protein kinase B and p70(S6)K by glucose and insulin-like growth factor 1 in pancreatic beta-cells (INS-1) (2001) Journal of Biological Chemistry, 276 (24), pp. 21110-21120Dumas, B.T., Watson, W.A., Biggs, H.G., Albumin standards and the measurement of serum albumin with bromcresol green. 1971 (1997) Clinica Chimica Acta, 258 (1), pp. 21-30Escriva, F., Kergoat, M., Bailbe, D., Pascual-Leone, A.M., Portha, B., Increased insulin action in the rat after protein malnutrition early in life (1991) Diabetologia, 34 (8), pp. 559-564Escriva, F., Rodriguez, C., Cacho, J., Alvarez, C., Portha, B., Pascual-Leone, A.M., Glucose utilization and insulin action in adult rats submitted to prolonged food restriction (1992) American Journal of Physiology, 263 (1 PART 1), pp. E1-E7Fafournoux, P., Bruhat, A., Jousse, C., Amino acid regulation of gene expression (2000) Biochemical Journal, 351 (PART 1), pp. 1-12Ferreira, F., Barbosa, H.C., Stoppiglia, L.F., Delghingaro-Augusto, V., Pereira, E.A., Boschero, A.C., Carneiro, E.M., Decreased insulin secretion in islets from rats fed a low protein diet is associated with a reduced PKAalpha expression (2004) Journal of Nutrition, 134 (1), pp. 63-67Ferreira, F., Filiputti, E., Arantes, V.C., Stoppiglia, L.F., Araujo, E.P., Delghingaro-Augusto, V., Latorraca, M.Q., Carneiro, E.M., Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase calpha expression (2003) Journal of Nutrition, 133 (3), pp. 695-699Foufelle, F., Girard, J., Ferre, P., Glucose regulation of gene expression (1998) Current Opinion in Clinical Nutrition and Metabolic Care, 1 (4), pp. 323-328Gatward, N., Anorexia nervosa: an evolutionary puzzle (2007) European Eating Disorders Review, 15 (1), pp. 1-12Hannan, K.M., Thomas, G., Pearson, R.B., Activation of S6K1 (p70 ribosomal protein S6 kinase 1) requires an initial calcium-dependent priming event involving formation of a high-molecular-mass signalling complex (2003) Biochemical Journal, 370 (PART 2), pp. 469-477Harper, A.E., Rogers, Q.R., Amino acid imbalance (1965) The Proceedings of the Nutrition Society, 24 (2), pp. 173-190Hashizume, K., Suzuki, S., Komatsu, A., Hiramatsu, K., Mori, J., Yamazaki, M., Takeda, T., Ichikawa, K., Administration of recombinant human growth hormone normalizes GH-IGF1 axis and improves malnutrition-related disorders in patients with anorexia nervosa (2007) Endocrine Journal, 54 (2), pp. 319-327Heard, C.R., The effects of protein-energy malnutrition on blood glucose homeostasis (1978) World Review of Nutrition and Dietetics, 30, pp. 107-147Heard, C.R., Frangi, S.M., Wright, P.M., Biochemical characteristics of different forms of protein-energy malnutrition in rats (1973) The Proceedings of the Nutrition Society, 32 (1), pp. 47AJousse, C., Bruhat, A., Fafournoux, P., Amino acid regulation of gene expression (1999) Current Opinion in Clinical Nutrition and Metabolic Care, 2 (4), pp. 297-301Jousse, C., Bruhat, A., Ferrara, M., Fafournoux, P., Evidence for multiple signaling pathways in the regulation of gene expression by amino acids in human cell lines (2000) Journal of Nutrition, 130 (6), pp. 1555-1560Kilberg, M.S., Hutson, R.G., Laine, R.O., Amino acid-regulated gene expression in eukaryotic cells (1994) FASEB Journal, 8 (1), pp. 13-19Latorraca, M.Q., Reis, M.A., Carneiro, E.M., Mello, M.A., Velloso, L.A., Saad, M.J., Boschero, A.C., Protein deficiency and nutritional recovery modulate insulin secretion and the early steps of insulin action in rats (1998) Journal of Nutrition, 128 (10), pp. 1643-1649Li, C., Najafi, H., Daikhin, Y., Nissim, I.B., Collins, H.W., Yudkoff, M., Matschinsky, F.M., Stanley, C.A., Regulation of leucine-stimulated insulin secretion and glutamine metabolism in isolated rat islets (2003) Journal of Biological Chemistry, 278 (5), pp. 2853-2858Malaisse, W.J., Sener, A., Mahy, M., The stimulus-secretion coupling of glucose-induced insulin release. Sorbitol metabolism in isolated islets (1974) European Journal of Biochemistry, 47 (2), pp. 365-370Muller, O., Krawinkel, M., Malnutrition and health in developing countries (2005) CMAJ. Canadian Medical Association Journal, 173 (3), pp. 279-286Muller, O., Becher, H., Malnutrition and childhood mortality in developing countries (2006) Lancet, 367 (9527), p. 1978Pegorier, J.P., Regulation of gene expression by fatty acids (1998) Current Opinion in Clinical Nutrition and Metabolic Care, 1 (4), pp. 329-334Pende, M., Kozma, S.C., Jaquet, M., Oorschot, V., Burcelin, R., Le Marchand-Brustel, Y., Klumperman, J., Thomas, G., Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice (2000) Nature, 408 (6815), pp. 994-997Peng, Y., Meliza, L.L., Vavich, M.G., Kemmerer, A.R., Effects of amino acid imbalance and protein content of diets on food intake and preference of young, adult, and diabetic rats (1975) Journal of Nutrition, 105 (11), pp. 1395-1404Proud, C.G., Denton, R.M., Molecular mechanisms for the control of translation by insulin (1997) Biochemical Journal, 328 (PART 2), pp. 329-341Reeves, P.G., Nielsen, F.H., Fahey Jr., G.C., AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet (1993) Journal of Nutrition, 123 (11), pp. 1939-1951Reis, M.A., Carneiro, E.M., Mello, M.A., Boschero, A.C., Saad, M.J., Velloso, L.A., Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats (1997) Journal of Nutrition, 127 (3), pp. 403-410Richardson, L.R., Hale, F., Ritchey, S.J., Effect of fasting and level of dietary protein on free amino acids in pig plasma (1965) Journal of Animal Science, 24, pp. 368-372Satin, L.S., Kinard, T.A., Neurotransmitters and their receptors in the islets of Langerhans of the pancreas: what messages do acetylcholine, glutamate, and GABA transmit? (1998) Endocrine, 8 (3), pp. 213-223Scott, A.M., Atwater, I., Rojas, E., A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans (1981) Diabetologia, 21 (5), pp. 470-475Shima, H., Pende, M., Chen, Y., Fumagalli, S., Thomas, G., Kozma, S.C., Disruption of the p70(s6k)/p85(s6k) gene reveals a small mouse phenotype and a new functional S6 kinase (1998) Embo Journal, 17 (22), pp. 6649-6659Srinivasan, M., Aalinkeel, R., Song, F., Lee, B., Laychock, S.G., Patel, M.S., Adaptive changes in insulin secretion by islets from neonatal rats raised on a high-carbohydrate formula (2000) American Journal of Physiology: Endocrinology and Metabolism, 279 (6), pp. E1347-E1357Srinivasan, M., Song, F., Aalinkeel, R., Patel, M.S., Molecular adaptations in islets from neonatal rats reared artificially on a high carbohydrate milk formula (2001) Journal of Nutritional Biochemistry, 12 (10), pp. 575-584Swenne, I., Borg, L.A., Crace, C.J., Schnell Landstrom, A., Persistent reduction of pancreatic beta-cell mass after a limited period of protein-energy malnutrition in the young rat (1992) Diabetologia, 35 (10), pp. 939-945Swenne, I., Crace, C.J., Milner, R.D., Persistent impairment of insulin secretory response to glucose in adult rats after limited period of protein-calorie malnutrition early in life (1987) Diabetes, 36 (4), pp. 454-458Tang, S., Beharry, S., Durie, P.R., Postnatal development of the rat exocrine pancreas. II. Effects of protein-calorie malnutrition on amylase secretion and CCK receptor binding (1997) Pancreas, 15 (4), pp. 335-344Towle, H.C., Metabolic regulation of gene transcription in mammals (1995) Journal of Biological Chemistry, 270 (40), pp. 23235-23238Vaulont, S., Kahn, A., Transcriptional control of metabolic regulation genes by carbohydrates (1994) Faseb Journal, 8 (1), pp. 28-35Wagner, J.E., Yamanaka, W., Typpo, J.T., Kusewitt, D.F., Pathological changes associated with dietary protein deficiency in guinea pigs (1977) Archivos Latinoamericanos de Nutrición, 27 (1), pp. 17-31Weinkove, C., Weinkove, E.A., Pimstone, B.L., Glucose tolerance and insulin release in malnourished rats (1976) Clinical Science and Molecular Medicine, 50 (3), pp. 153-163Xu, G., Kwon, G., Cruz, W.S., Marshall, C.A., McDaniel, M.L., Metabolic regulation by leucine of translation initiation through the mTOR-signaling pathway by pancreatic beta-cells (2001) Diabetes, 50 (2), pp. 353-360Xu, G.G., Gao, Z.Y., Borge Jr., P.D., Jegier, P.A., Young, R.A., Wolf, B.A., Insulin regulation of beta-cell function involves a feedback loop on SERCA gene expression, Ca(2+) homeostasis, and insulin expression and secretion (2000) Biochemistry, 39 (48), pp. 14912-14919Xu, G.G., Gao, Z.Y., Borge Jr., P.D., Wolf, B.A., Insulin receptor substrate 1-induced inhibition of endoplasmic reticulum Ca2+ uptake in beta-cells. Autocrine regulation of intracellular Ca2+ homeostasis and insulin secretion (1999) Journal of Biological Chemistry, 274 (25), pp. 18067-18074Zamboni, G., Dufillot, D., Antoniazzi, F., Valentini, R., Gendrel, D., Tato, L., Growth hormone-binding proteins and insulin-like growth factor-binding proteins in protein-energy malnutrition, before and after nutritional rehabilitation (1996) Pediatric Research, 39 (3), pp. 410-41
Restoration of insulin secretion in pancreatic islets of protein-deficient rats by reduced expression of insulin receptor substrate (IRS)-1 and IRS-2
Autocrine and paracrine insulin signaling may participate in the fine control of insulin secretion. In the present study, tissue distribution and protein amounts of the insulin receptor and its major substrates, insulin receptor substrate (IRS)-1 and IRS-2, were evaluated in a model of impaired glucose-induced insulin secretion, the protein-deficient rat. Immunoblot and RT-PCR studies showed that the insulin receptor and IRS-2 expression are increased, whilst IRS-1 protein and mRNA contents are decreased in pancreatic islets of protein-deficient rats. lmmunohistochemical studies revealed that the insulin receptor and IRS-1 and -2 are present in the great majority of islet cells; however, the greatest staining was localized at the periphery, suggesting a co-localization with non-insulin-secreting cells. Exogenous insulin stimulation of isolated islets promoted higher insulin receptor and IRS-1 and -2 tyrosine phosphorylation in islets from protein-deficient rats, as compared with controls. Moreover, insulin-induced IRS-1- and IRS-2-associated phosphatidylinositol 3-kinase activity are increased in islets of protein-deficient rats. The reduction of IRS-1 and IRS-2 protein expression in islets isolated from protein-deficient rats by the use of antisense IRS-1 or IRS-2 phosphorthioate-modified oligonucleotides partially re- stored glucose-induced insulin secretion. Thus, the impairment of insulin cell signaling through members of the IRS family of proteins in isolated rat pancreatic islets improves glucose-induced insulin secretion. The present data reinforced the role of insulin paracrine and autocrine signaling in the control of its own secretion.1811253
Decreased Cholinergic Stimulation Of Insulin Secretion By Islets From Rats Fed A Low Protein Diet Is Associated With Reduced Protein Kinase Cα Expression
Undernutrition has been shown to affect the autonomic nervous system, leading to permanent alterations in insulin secretion. To understand these interactions better, we investigated the effects of carbamylcholine (CCh) and phorbol 12-myristate 13-acetate (PMA) on insulin secretion in pancreatic islets from rats fed a normal (17%; NP) or low (6%; LP) protein diet for 8 wk. Isolated islets were incubated for 1 h in Krebs-bicarbonate solution containing 8.3 mmol glucose/L, with or without PMA (400 nmol/L) and CCh. Increasing concentrations of CCh (0.1-1000 μmol/L) dose dependently increased insulin secretion by islets from both groups of rats. However, insulin secretion by islets from rats fed the NP diet was significantly higher than that of rats fed the LP diet, and the dose-response curve to CCh was shifted to the right in islets from rats fed LP with a 50% effective concentration (EC50) of 2.15 ± 0.7 and 4.64 ± 0.1 μmol CCh/L in islets of rats fed NP and LP diets, respectively (P < 0.05). PMA-induced insulin secretion was higher in islets of rats fed NP compared with those fed LP. Western blotting revealed that the protein kinase (PK)Cα and phospholipase (PL)Cβ1 contents of islets of rats fed LP were 30% lower than those of islets of rats fed NP (P < 0.05). In addition, PKCα mRNA expression was reduced by 50% in islets from rats fed LP. In conclusion, a reduced expression of PKCα and PLCβ1, may be involved in the decreased insulin secretion by islets from LP rats after stimulation with CCh and PMA.1333695699Becker, D.J., The endocrine responses to protein calorie malnutrition (1983) Annu. Rev. Nutr., 3, pp. 187-212Escriva, F., Rodriguez, C., Cacho, J., Alvarez, C., Portha, B., Pascual-Leone, A.M., Glucose utilization and insulin action in adult rats submitted to prolonged food restriction (1992) Am. J. Physiol., 263, pp. E1-E7Heard, C.R., The effects of protein-energy malnutrition on blood glucose homeostasis (1978) World Rev. Nutr. Diet., 30, pp. 107-147Okitolonda, W., Brichard, S.M., Henquin, J.C., Repercussions of chronic protein-calorie malnutrition on glucose homeostasis in the rat (1987) Diabetologia, 30, pp. 946-951Picarel-Blanchot, F., Alvarez, C., Bailbe, D., Pascual-Leone, A.M., Portha, B., Changes in insulin action and insulin secretion in the rat after dietary restriction early in life: Influence of food restriction versus low-protein food restriction (1995) Metabolism, 44, pp. 1519-1526Escriva, F., Kergoat, M., Bailbe, D., Pascual-Leone, A.M., Portha, B., Increased insulin action in the rat after protein malnutrition early in life (1991) Diabetologia, 34, pp. 559-564Levine, L.S., Wright, P.G., Marcus, F., Failure to secrete immunoreactive insulin by rats fed a low protein diet (1983) Acta Endocrinol., 102, pp. 240-245Swenne, I., Crace, C.J., Milner, R.D., Persistent impairment of insulin secretory response to glucose in adult rats after limited period of protein-calorie malnutrition early in life (1987) Diabetes, 36, pp. 454-458Swenne, I., Crace, C.J., Jansson, L., Intermittent protein-calorie malnutrition in the young rat causes long-term impairment of the insulin secretory response to glucose in vitro (1988) J. Endocrinol., 118, pp. 295-302Swenne, I., Borg, L.A., Crace, C.J., Schnell-Landstrom, A., Persistent reduction of pancreatic beta-cell mass after a limited period of protein-energy malnutrition in the young rat (1992) Diabetologia, 35, pp. 939-945Leon-Quinto, T., Magnan, C., Portha, B., Altered activity of the autonomous nervous system as a determinant of the impaired beta-cell secretory response after protein-energy restriction in the rat (1998) Endocrinology, 139, pp. 3382-3389Kelley, G.G., Zawalich, K.C., Zawalich, W.S., Synergistic interaction of glucose and neurohumoral agonists to stimulate islet phosphoinositide hydrolysis (1995) Am. J. Physiol., 269, pp. E575-E582Verspohl, E.J., Herrmann, K., Involvement of G proteins in the effect of carbachol and cholecystokinin in rat pancreatic islets (1996) Am. J. Physiol., 271, pp. E65-E72Verspohl, E.J., Tacke, R., Mutschler, E., Lambrecht, G., Muscarinic receptor subtypes in rat pancreatic islets: Binding and functional studies (1990) Eur. J. Pharmacol., 178, pp. 303-311Persaud, S.J., Jones, P.M., Howell, S.L., Activation of protein kinase C is essential for sustained insulin secretion in response to cholinergic stimulation (1991) Biochim. Biophys. Acta, 1091, pp. 120-122Bansal, S.K., Jaiswal, A.S., Kathayat, R., Basir, S.F., Misra, U.K., Effect of dietary protein manipulation on translocation of protein kinase C activity in various tissues of rats (1996) Indian J. Exp. Biol., 34, pp. 197-200Reis, M.A.B., Carneiro, E.M., Mello, M.A.R., Boschero, A.C., Saad, M.A.J., Velloso, L.A., Glucose-induced insulin secretion is impaired and insulin-induced phosphorylation of the insulin receptor and insulin receptor substrate-1 are increased in protein-deficient rats (1997) J. Nutr., 127, pp. 403-410Doumus, B.T., Watson, W.A., Biggs, H.G., Albumin standards and measurements of serum albumin with bromocresol green (1971) Clin. Chim. Acta, 31, pp. 87-96Heard, C.R., Frangi, S.M., Wright, P.M., McCartney, P.R., Biochemical characteristics of different forms of protein-energy malnutrition: An experimental model using young rats (1997) Br. J. Nutr., 37, pp. 1-21Weinkove, C., Weinkove, E.A., Pimstone, B.L., Glucose tolerance and insulin release in malnourished rats (1976) Clin. Sci. Mol. Med., 50, pp. 153-163Bordin, S., Boschero, A.C., Carneiro, E.M., Atwater, I., Ionic mechanisms involved in the regulation of insulin secretion by muscarinic agonists (1995) J. Membr. Biol., 148, pp. 177-184Scott, A.M., Atwater, I., Rojas, E., A method for the simultaneous measurement of insulin release and B cell membrane potential in single mouse islets of Langerhans (1981) Diabetologia, 21, pp. 470-475Eickhoff, B., Korn, B., Schick, M., Poustka, A., Van der Bosch, J., Normalization of array hybridization experiments in differential gene expression analysis (1999) Nucleic Acids Res., 27, pp. e33Claeyssens, S., Lavoinne, A., Vaillant, C., Rakotomanga, J.A., Bois-Joyeux, B., Peret, J., Metabolic changes during early starvation in rats fed a low-protein diet in the postweaning growth period (1992) Metabolism, 41, pp. 722-727Davies, M.J., Rayman, G., Grenfell, A., Gray, I.P., Day, J.L., Hales, C.N., Loss of the first phase insulin response to intravenous glucose in subjects with persistent impaired glucose tolerance (1994) Diabetes Med., 11, pp. 432-436Del Prato, S., Tiengo, A., The importance of first-phase insulin secretion: Implications for the therapy of type 2 diabetes mellitus (2001) Diabetes Metab. Res. Rev., 17, pp. 164-174Kahn, S.E., Montgomery, B., Howel, W., Ligueros-Saylan, M., Hsu, C.H., Devineni, D., McLeod, J.F., Foley, J.E., Importance of early phase insulin secretion to intravenous glucose tolerance in subjects with type 2 diabetes mellitus (2001) J. Clin. Endocrinol. Metab., 86, pp. 5824-5829Boschero, A.C., Szpak-Glasman, M., Carneiro, E.M., Bordin, S., Paul, I., Rojas, E., Atwater, I., Oxotremorine-m potentiation of glucose-induced insulin release from rat islets involves M3 muscarinic receptors (1995) Am. J. Physiol., 268, pp. E336-E342Henquin, J.C., Nenquin, M., The muscarinic receptor subtype in mouse pancreatic B-cells (1988) FEBS Lett., 236, pp. 89-92Woods, S.C., Porte D., Jr., Neural control of the endocrine pancreas (1974) Physiol. Rev., 54, pp. 596-619Henquin, J.C., Jonas, J.C., Gilon, P., Functional significance of Ca2+ oscillations in pancreatic beta cells (1998) Diabetes Metab., 24, pp. 30-36Santos, R.M., Rojas, E., Muscarinic receptor modulation of glucose-induced electrical activity in mouse pancreatic B-cells (1989) FEBS Lett., 249, pp. 411-417Verchere, C.B., Kwok, Y.N., Brown, J.C., Modulation of acetylcholine-stimulated insulin release by glucose and gastric inhibitory polypeptide (1991) Pharmacology, 42, pp. 273-282Prentki, M., Matschinsky, F.M., Ca2+, cAMP, and phospholipid-derived messengers in coupling mechanisms of insulin secretion (1987) Physiol. Rev., 67, pp. 1185-1248Berggren, P.O., Arkhammar, P., Nilsson, T., Activation of protein kinase C assists insulin producing cells in recovery from raised cytoplasmic calcium by stimulating calcium efflux (1989) Biochem. Biophys. Res. Commun., 165, pp. 416-421Jones, P.M., Persaud, S.J., Howell, S.L., Protein kinase C and the regulation of insulin secretion from pancreatic B cells (1991) J. Mol. Endocrinol., 6, pp. 121-127Wollheim, C.B., Dunne, M.J., Peter-Riesch, B., Bruzzone, R., Pozzan, T., Petersen, O.H., Activators of protein kinase C depolarize insulin-secreting cells by closing K+ channels (1988) EMBO J., 7, pp. 2443-2449Yada, T., Russo, L.L., Sharp, G.W., Phorbol ester-stimulated insulin secretion by RINm5F insulinoma cells is linked with membrane depolarization and an increase in cytosolic free Ca2+ concentration (1989) J. Biol. Chem., 264, pp. 2455-2462Wei, Y., Tae, N., Tatsuya, F., Hiroyoshi, H., Takao, S., Yasuharu, S., Ighiro, N., Synergism of protein kinase A, protein kinase C, and myosin light-chain kinase in the secretory cascade of the pancreatic B-cell (2000) Diabetes, 49, pp. 945-952Easom, R.A., Hughes, J.H., Landt, M., Wolf, B.A., Turk, J., McDaniel, M.L., Comparison of effects of phorbol esters and glucose on protein kinase C activation and insulin secretion in pancreatic islets (1989) Biochem. J., 264, pp. 27-33Persaud, S.J., Jones, P.M., Sugden, D., Howell, S.L., Translocation of protein kinase C in rat islets of Langerhans. Effects of a phorbol ester, carbachol and glucose (1989) FEBS Lett., 245, pp. 80-84Arkhammar, P., Juntti-Berggren, L., Larsson, O., Welsh, M., Nanberg, E., Sjoholm, A., Kohler, M., Berggren, P.-O., Protein kinase C modulates the insulin secretory process by maintaining a proper function of the beta-cell voltage-activated Ca2+ channels (1994) J. Biol. Chem., 269, pp. 2743-2749Ganesan, S., Calle, R., Zawalich, K., Smallwood, J.I., Zawalich, W.S., Rasmussen, H., Glucose-induced translocation of protein kinase C in rat pancreatic islets (1990) Proc. Natl. Acad. Sci. U.S.A., 87, pp. 9893-9897Zaitsev, S.V., Efendic, S., Arkhammar, P., Bertorello, A.M., Berggren, P.-O., Dissociation between changes in cytoplasmic free Ca2+ concentration and insulin secretion as evidenced from measurements in mouse single pancreatic islets (1995) Proc. Natl. Acad. Sci. U.S.A., 92, pp. 9712-9716Nakamura, J., Suda, T., Ogawa, Y., Takeo, T., Suga, S., Wakui, M., Protein kinase C-dependent and -independent inhibition of Ca2+ influx by phorbol ester in rat pancreatic beta-cells (2001) Cell. Signalling, 13, pp. 199-20
Decreased cholinergic stimulation of insulin secretion by islets from rats fed a low protein diet is associated with reduced protein kinase C alpha expression
Undernutrition has been shown to affect the autonomic nervous system, leading to permanent alterations in insulin secretion. To understand these interactions better, we investigated the effects of carbamyl-choline (CCh) and phorbol 12-myristate 13-acetate (PMA) on insulin secretion in pancreatic islets from rats fed a normal (17%; NP) or low (6%; LP) protein diet for 8 wk. Isolated islets were incubated for 1 h in Krebs-bicarbonate solution containing 8.3 mmol glucose/L, with or without PMA (400 nmoI/Q and CCh. Increasing concentrations of CCh (0.1 -1000 mumol/L) dose dependently increased insulin secretion by islets from both groups of rats. However, insulin secretion by islets from rats fed the NP diet was significantly higher than that of rats fed the LIP diet, and the dose-response curve to CCh was shifted to the right in islets from rats fed LIP with a 50% effective concentration (EC50) of 2.15 +/- 0.7 and 4.64 +/- 0.1 mumol CCh/L in islets of rats fed NP and LP diets, respectively (P < 0.05). PMA-induced insulin secretion was higher in islets of rats fed NP compared with those fed LIP. Western blotting revealed that the protein kinase (PK)Calpha and phospholipase (PL)Cbeta(1) contents of islets of rats fed LP were 30% lower than those of islets of rats fed NP (P < 0.05). In addition, PKCalpha mRNA expression was reduced by 50% in islets from rats fed LIP. In conclusion, a reduced expression of PKCa and PLCbeta(1), may be involved in the decreased insulin secretion by islets from LIP rats after stimulation with CCh and PMA. J. Nutr. 133: 695-699, 2003.133369569
Exercise at anaerobic threshold intensity and insulin secretion by isolated pancreatic islets of rats
To evaluate the effect of acute exercise and exercise training at the anaerobic threshold (AT) intensity on aerobic conditioning and insulin secretion by pancreatic islets, adult male Wistar rats were submitted to the lactate minimum test (LMT) for AT determination. Half of the animals were submitted to swimming exercise training (trained), 1 h/day, 5 days/week during 8 weeks, with an overload equivalent to the AT. The other half was kept sedentary. At the end of the experimental period, the rats were submitted to an oral glucose tolerance test and to another LMT. Then, the animals were sacrificed at rest or immediately after 20 minutes of swimming exercise at the AT intensity for pancreatic islets isolation. At the end of the experiment mean workload (% bw) at AT was higher and blood lactate concentration (mmol/L) was lower in the trained than in the control group. Rats trained at the AT intensity showed no alteration in the areas under blood glucose and insulin during OGTT test. Islet insulin content of trained rats was higher than in the sedentary rats while islet glucose uptake did not differ among the groups. The static insulin secretion in response to the high glucose concentration (16.7 mM) of the sedentary group at rest was lower than the sedentary group submitted to the acute exercise and the inverse was observed in relation to the trained groups. Physical training at the AT intensity improved the aerobic condition and altered insulin secretory pattern by pancreatic islets