109 research outputs found
Association of Dioxin and Other Persistent Organic Pollutants (POPs) with Diabetes: Epidemiological Evidence and New Mechanisms of Beta Cell Dysfunction.
The incidence of type 2 diabetes significantly increases with age. The relevance of this association is dramatically magnified by the concomitant global aging of the population, but the underlying mechanisms remain to be fully elucidated. Here, some recent advances in this field are reviewed at the level of both the pathophysiology of glucose homeostasis and the cellular senescence of pancreatic islets. Overall, recent results highlight the crucial role of beta-cell dysfunction in the age-related impairment of pancreatic endocrine function and delineate the possibility of new original therapeutic interventions
Mitochondrial myopathy in rats fed with a diet containing beta-guanidine propionic acid, an inhibitor of creatine entry in muscle cells.
In rats with phosphoryl-creatine depletion (fed a standard Randoin-Causeret diet
containing 1% beta-guanidine propionic acid) abnormal mitochondria were observed
in slow skeletal muscles, often containing paracrystalline inclusions very like
those induced by ischaemia or mitochondrial poisons and in human mitochondrial
myopathy
Effects of the administration of angiotensin II on cardiac glycogen metabolism in the rat.
Changes in glycogen metabolism after an intravenous injection of angiotensin II
were investigated in the left and right ventricles of the rat heart, as a
function of location within the ventricular wall. Hearts were cut into
100-microns thin section, all of which were analysed for glycogen content,
glucose incorporation into glycogen and 2-deoxyglucose uptake and phosphorylation
after the intravenous injection of 14C-labelled sugar. In control hearts,
glycogen levels were uniform across the wall in both ventricles, while the rate
of sugar uptake and phosphorylation, and that of glucose incorporation into
glycogen, were significantly higher in the subendocardial myocardium of the left
ventricular wall. After angiotensin II administration, heart glycogen levels
decreased slightly in the left, but not in the right ventricle, while
2-deoxyglucose uptake and phosphorylation, and glucose incorporation into
glycogen, increased 2,5- and 5-fold, respectively. With regard to the
distribution across the wall of the left ventricle after angiotensin
administration, glycogen levels and glucose incorporation into glycogen were
uniformly distributed, whereas sugar phosphorylation was still higher in the
subendocardium
Pancreatic Beta Cell Identity in Humans and the Role of Type 2 Diabetes
Pancreatic beta cells uniquely synthetize and release insulin. Specific molecular, functional as well as ultrastructural traits characterize their insulin secretion properties and survival phenotype. In this review we focus on human islet/beta cells, and describe the changes that occur in type 2 diabetes and could play roles in the disease as well as represent possible targets for therapeutical interventions. These include transcription factors, molecules involved in glucose metabolism and insulin granule handling. Quantitative and qualitative insulin release patterns and their changes in type 2 diabetes are also associated with ultrastructural features involving the insulin granules, the mitochondria, and the endoplasmic reticulum
Age-dependent reduction in GLUT-2 levels is correlated with the impairment of the insulin secretory response in isolated islets of Sprague-Dawley rats.
In this study we have investigated the insulin secretory response to glucose and other secretagogues (2-ketoisocaproate, 3-isobutyl-1-methyl-xanthine and arginine) of pancreatic islets isolated from Sprague-Dawley rats of various ages (from 2 to 28 months). Our results showed a significant decline in the glucose-stimulated insulin secretion, starting at 12 months of age. On the other hand, the response to non-glucose secretagogues (and mainly to 2-ketoisocaproate) was less impaired with advancing age than that to glucose. We also observed a progressive age-related decline of protein levels of the glucose transporter GLUT-2 in pancreatic islets, which was temporally concomitant and quantitatively comparable with the beta-cell alteration in glucose responsiveness (-40/50%). Finally, we observed a significant increase of the islets insulin content in older rats with respect to younger animals. We conclude that in the islet of older rats the impaired capability to respond to glucose could be dependent, at least in part, on the age-dependent reduction in GLUT-2 and could be compensated by mechanisms including a preserved responsiveness to non-glucose secretagogues and/or the development of islet hypertrophy
Transmural gradient of glycogen metabolism in the normal rat left ventricle.
The changes of glycogen metabolism with the location of tissue within the
ventricle wall have been explored in the rat myocardium. The hearts were cut in
100 microns thick serial sections and all sections were analyzed for their
content in glycogen, glucose-6-phosphate, UDPG and glycogen enzymes and for
glucose incorporation into glycogen and for the 2-deoxyglucose uptake after the
intravenous injection of the 14C-labelled sugars. The rate of glycogen turnover
was significantly higher in the subendocardial myocardium (P less than 0.01) and
the levels of glucose-6-phosphate and the total (i.e. a + b) activity of glycogen
phosphorylase were significantly higher in the subepicardial tissue (P less than
0.01 in both instances). No significant transmural gradient of UDPG was found and
transmural changes of total (i.e. I + D) synthase activity were barely
significant. These changes in glycogen metabolism may be related to regional
differences in the cardiac work load and to a differentiation of the
subendocardial and subepicardial heart fibers
Effects of low-dose VOSO4 on age-related changes in glucose homeostasis in rats
The effects of low doses of vanadyl sulfate (0.2 mg/ml in the drinking water) on
the age-related impairment of glucose homeostasis in Sprague-Dawley rats were
investigated. VOSO(4) administration was initiated in 5-month-old animals and
lasted 3 months. Thus, in 8-month-old rats, we investigated glucose metabolism in
vivo and insulin secretory function in vitro. Results showed that VOSO(4) allowed
the disposal of an oral glucose load at lower insulin levels than in age-matched
controls. No significant changes were found in muscle glucose transporter
(GLUT-4) levels or in glycogen content upon VOSO(4) treatment. Islets isolated
from VOSO(4)-treated rats released less insulin than control islets, but showed a
better preserved sensitivity to secretagogues, in terms of incremental release
over basal release, secretory efficiency, and maintenance of the priming effect
of glucose. In conclusion, chronic low-dose VOSO(4) treatment facilitates insulin
action by a mechanism independent of muscle GLUT-4 levels and helps preserve the
appropriate sensitivity of beta cells to stimuli, thereby preventing
age-dependent functional alterations
Protective role of dehydroascorbate in rat liver ischemia-reperfusion injury
BACKGROUND:
Oxidative stress plays an important role in liver ischemia/reperfusion (I/R) injury. Thus, enhancing the liver antioxidant capacity could be a promising therapeutic strategy. Ascorbate (AA) is considered the perfect antioxidant, but its therapeutic efficacy is greatly limited by its slow achievement of high intracellular levels. This might be circumvented by administering dehydroascorbate (DHA), which presents a several-fold greater uptake than AA, and undergoes rapid intracellular reduction to AA. Thus, our aim was to assess the protective role of DHA in liver I/R injury.
MATERIALS AND METHODS:
Wistar rats (200-300 g bw) were pretreated iv with different doses of AA or DHA 20 min before liver ischemia, followed by 6 h reperfusion. Liver damage was assessed by biochemical and morphological indices.
RESULTS:
DHA pretreatment induced a rapid increase in liver ascorbate levels, significantly higher than findings for AA, without any significant reduction in glutathione levels. Liver damage during I/R in controls showed significant increases in serum transaminases and hepatic thiobarbituric acid reactive substances with alterations of liver morphology. DHA administration induced a clear, significant protection against I/R injury, whereas liver damage was only moderately prevented by AA.
CONCLUSIONS:
DHA might represent a simple, effective therapeutic option to prevent liver damage associated with ischemia/reperfusion
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