D. DEVILLE DE PERIERE

G. RIBES

JC EGEA

M. BOMBARA

NOVELLI M

P. MASIELLO

R. GROSS

English

NOVELLI, MICHELA

MASIELLO, PELLEGRINO

Archivio della Ricerca - Università di Pisa

Diab. Nutr. Metab. 10: 203-205, 1997READERS' FORUMIncrease of insulin-like immunoreactivity insubmandibular salivary glands ofdexamethasone-treated ageing ratsDear Sir,Previous reports showed that parotid and sub-mandibular salivary glands (SSG) of various ani-mal species, including man, contain an insulin-likeimmunoreactive factor (ILI) (1, 2) which can bindin vìtro to insulin receptors and exert several bio-logical activities of insulin, such as stimulation ofamino acid uptake and lipogenesis (3). This factoris likely to be synthesized in situ by cells of thè in-tercalated ducts (4), differently from most other hor-mones and growth factors present in thè salivaryglands, which are produced in thè granular convo-luted tubular cells (5, 6). We have previously re-ported that thè ILI content in rat SSG is maintainedthroughout lifetime (7) and is increased in strepto-zotocin-diabetic animals (8), In thè present workwe investigated whether SSG-ILI was also increasedin another type of experimental diabetes, inducedby glucocorticoids administration to ageing rats andcharacterized by augmented peripheral insulin re-sistance (9). Male Sprague-Dawley rats of 18months of age (620-680 g body weight) were sub-jected to a daily subcutaneous injection of dexam-ethasone (DEX) phosphate (0.125 mg/kg, dissolvedin saline) for 13 days. An age-matched untreatedgroup was used as contro!. Blood samples were col-lected from thè tail vein of conscious animals dur-ing thè experimental treatment for thè monitoringof plasma glucose and insulin levels. Twenty-fourhours after thè last DEX injection, thè rats wereanaesthetìzed with sodium pentobarbital (50 mg/kg)and SSG were dissected and homogenized. Themethods of extraction and evaluation of ILI havebeen previously described (3).Body weights of 18-month old rats decreased by20% after 13 days of DEX treatment and also adrenalgland weights were significantly reduced with re-spect to controls (p<Q.Ql) (Table 1). DEX-treatedanimals developed hyperglycaemia and marked hy-perinsulinaemia (4-5-foId increase over basai val-ues). Il should be noticed that some DEX-treatedrats remained normoglycaemic although most ofthem became markedly hyperglycaemìc.Figure 1 illustrates that thè ILI content of sub-mandibular glands increased significantly in DEXtreated animals with respect to untreated age-matchedcontrols, and that thè submandibular gland proteincontent was unchanged in control and DEX-treatedanimals respectively.Thus, ILI present in salivary glands can be modifiedby a glucocorticoid treatment leading to alterationof glucose homeostasis in ageing animals. This ob-servation is an additional example for thè possibil-ity for ILI content to be regulated, which was pre-viously found to be thè case in streptozotocin dia-betics rats where SSG-ILI levels increased after 4weeks duration of disease (8). In thè latter case, thèILI increase was interpreted as a compensatory adap-tation in insulin deficient diabetic syndrome whichmight help to preserve salivary gland function (10).Moreover DEX treatment of 18-month old rats,which was highly effective in ali animals as testi-fied by adrenal gland hypotrophy, led to a markedhyperglycaemia only in those animals in which thèintervening compensatory hyperinsulinaemia wasprobably insuffìcient to restore an already precari-ous glucose homeostasis. Indeed, it is likely thatDEX administration further aggravated a pre-exist-ing age-dependent state of insulin resistance in tar-get tissues, which has been reported to develop quiteearly during ageing (11).It cannot be excluded that thè increased ILI contentDiab. Nutr. Metab. 10: 203-205, 1997. © 1997, Editrice Kunis.DNM, Voi. 10, N. 4 203D. Deville de Périère, M. Novelli, M. Bombarci, et alTable 1 - Characteristics of 18 mo old Sprague-Dawley ratstreated with dexamethasone (DEX).Treatment Controls DEXBody weight (g)Before treatmentAfter treatmentAdrenal gland weight (mg)Glycaemia (mg/dl)Insulinaemìa (ng/ml)696±2671 0±1 923±3110±63.6±0.6731 ±23584±18"12±1**246±59*17.3±2.5**Mean±SEM of 6-7 determinations.*p<0.05, **p<0.01 vs controisfound in SSG of hyperinsulinaemic animals couldbe, at least in part, accounted for by trapped insulinthrough a ligand-receptor endocytotic process. How-ever, thè previously reported increase in ILI contentof SSG in streptozotocin-diabetic rats with negligi-ble circulating insulin levels (8) and thè directdemonstration of thè presence of insulin mRNA inthè mouse salivary glands (12), support thè as-sumption that most insulin-like material is synthe-sized in sita. On thè basis of thè common embry-ologic origin, structure and function of pancreatkand salivary tissues, it may be suggested that not on-ly pancreatic [3-cells but also ILI-producing cells insalivary glands could be stimulated by DEX treat-ment to produce more insulin or ILI as a compen-satory adaptation. However, it should also be re-minded that DEX is a well known inducer of geneexpression like other steroid hormones (13) and fi-10 - - 10 £Controis DEXFig. 1 - Insulin-like immunoreactivity (ILI) and protein con-tent in submandibular salivary glands of 18-mo old rats treat-ed with dexamethasone (DEX). Bars represent mean ± SEMof 14 determinations, *p<0.01 vs controis.nally, that increased ILI levels result from a directeffect of DEX treatment or rather from thè hormonalinduced insulin resistance remains to be determined.In summary we report here that, as in streptozotocindiabetic rats characterized by a drastic reduction ofinsulinaemia, ILI:.production in rat SSG is also en-hanced in DEX-induced diabetes, characterized byperipheral insulin resistance rather than drasticallyimpaired insulin secretion.D. Deville de Périère*, M. Novelli**,M. Bombara**, J.-C. Egèa*, R. Cross***,G. Ribes*** and P. Masiello***Laboratoire de Physiologie, Faculté d'Odontologie,**Istituto di Patologia Generale dell'Università di Pisa, Italia,and ***Laboratoire de Pharmacologie, UMR-CNRS 9921Montpellier, France.REFERENCES1. Murakami K., Taniguchi H., Babà S.: Presence of insulin-like immunoreactivity and its biosynthesis in rat and hu-man parotid gland. Diabefologìa 22: 358-361, 1982.2. Patel D.G., Begum N., Smith P.H.: Insulin-like material inparotid and submaxillary salivary glands of normal and di-abetic adult male mice. Diabetes 35: 753-758, 1986.3. Taoois M., Deville de Périère D., Hillaire-Buys D., Der-ouet M., Cross R., Simon J., Ribes G.: Biologìcal activi-ty of immunoreactive insulin-like activity extracted fromrat submandibular gland. Am. J. Phvsiol. 32: E277-E282,1995.4. Smith P.H., Toms B.B.: Immunocytochemical localizationof insulin- and glucagon-like peptides in rat salivary glands.J. Histochem. Cytochem. 34: 627-632, 1986.5. Barka T.: Biologically active polypeptides in thè sub-mandìbular gland. J. Histochem. Cvtochem. 28: 836-859,1980.6. Watson A.Y., Anderson J.K., Siminoski K., Mole J.E.,Murphy R.A.: Cellular and subcellular colocalization ofnerve growth factor and epidermal growth factor in mousesubmandibular glands. Anat. Ree. 213: 365-376, 1985.7. Deville de Périère D., Bombara M., Egea J.-C., NovelliM., Ribes G., Masiello P.: Age-dependent changes in in-sulin-like immunoreactivity in rat submandibular salivaryglands. Eur. J. Orai Sci. 104: 630-633, 1996.8. Deville de Périère D., Hillaire-Buys D., Cross R., PuechR., Arancibia S.: Increases in concentrations of somato-statin- and insulin-like immunoreactivities in submandibularsalivary gland of diabetic rats: effect of insulin treatment.Acta EndocrinoL (Copenh.) 120: 790-794, 1989.9. McMahon M., Gerich J., Rizza. R.: Effects of glucocorti-coids on carbohydrate metabolism. Diabetes Metab. Rev.4: 17-30, 1988.10. Hu Y., Nakagawa Y., Purushotham K.R., Humphreys-Be-204 DNM, Voi. 10, N. 4Jnsulin-lìke factor in salivary glandsher M.G.: Functional changes in salivary glands of au-toimmune disease-prone NOD mice. Am. J. Physiol. 263:E607-E614, 1992.11. Goodman M., Dluz S., McElaney M., Belur E., RudermanN.: Glucose uptake and insulin sentivity in rat muscle:change during 3-96 weeks of age. Am. J. Physiol. 244 (En-docrinol. Metab. 7): E93-E100, 1983.12. Kerr M., Lee A., Wang P., Purushotham K.R., Ghegini N,,Yamamoto H., Humphreys-Beher M.G.: Detection of insulinand insulin-tike growth factors I and H in saliva and potentialsynthesis in thè salivary glands of mice. Effects of type 1 di-abetes mellitus. Biochem. PhannacoL 49: 1521-1531,1995.13. Lucas P.C., Granner O.K.: Hormone response domains ingene transcription. Annu, Rev. Biochem. 61: 1131-1173,1992.DNM, Voi. 10, N. 4 205

Increase of insulin-like immunoreactivity in submandibular salivary glands of dexamethasone-treated ageing rats

https://arpi.unipi.it/bitstream/11568/176656/1/Diab%20Nutr%20Metab%201997.pdf

Increase of insulin-like immunoreactivity in submandibular salivary glands of dexamethasone-treated ageing rats

Abstract

Similar works

Full text

Available Versions

Archivio della Ricerca - Università di Pisa