Vanadate Induction of Pancreatic Amylase mRNA in Diabetic Rats

Abstract

Amylase activity and mRNA abundance are reduced to < 1 % of normal levels in diabetic rat pancreas. Administration of vanadate in drinking water restored normal amylase activity and amylase mRNA levels. These results demonstrate an effect of vanadate on pancreatic acinar cells and suggest that vanadate can mimic the effect of insulin on transcription of the pancreatic amylase gene. Diabetes 39:757-59,1990 I norganic vanadate has the remarkable property of reproducing several of the biological effects of insulin in cultured cells and intact animals (for review, see refs. 1 -3). In diabetic rats, oral administration of vanadate results in normalized blood glucose levels (1,4). The correction of hyperglycemia is accompanied by vanadate-stimulated glucose uptake in muscle and liver (5). In the liver of diabetic rats, vanadate mimics the effect of insulin on levels of glucokinase and fructose-2,6-bisphosphate activity (6,7). Molecular characterization of the insulinlike activities of vanadate is the subject of active investigation in several laboratories.The induction of pancreatic amylase in diabetic rodents is one of the well-characterized responses to insulin (8,9). Amylase transcripts account for 20% of total mRNA in the normal pancreas. When animals are given streptozocin or other diabetogenic agents, the abundance of the amylase mRNA is reduced to < 1 % of normal (10-12). Normal levels of amylase mRNA can be restored by administration of insulin. The response to insulin is dependent on an enhancer element in the 5'-flanking region of the amylase gene (13; unpublished observations). is one of the largest effects of insulin on a specific mRNA (14). In this study, we investigate the ability of vanadate to replace insulin in the regulation of pancreatic amylase. RESEARCH DESIGN AND METHODSDiabetes was induced in male Wistar rats weighing 325-340 g by injection of freshly prepared streptozocin in citrate buffer, pH 4.5, at a dose of 60 mg/kg body wt i.p. Blood glucose levels were determined 48 h after streptozocin administration with an Accu-Check II blood glucose monitor. Animals with blood glucose concentrations >17 mM were included in the study. Untreated controls were matched for age and weight.Sodium orthovanadate (0.8 mg/ml) was administered in drinking water. Treatment was initiated 7 days after administration of streptozocin and continued for 26 days. Blood glucose levels were determined at 4-day intervals. Animals that responded to vanadate with reduction of blood glucose concentrations to <11 mM were included in the study. Animals were weighed daily, and weight loss of >15 g was treated by injection of 10 ml lactated Ringer's bicarbonate solution s.c. (0.84%). Rehydration was required by -2 0 % of the rats, usually during the 1st wk of vanadate treatment.Amylase activity of pancreatic homogenates was assayed by measurement of reducing groups generated from soluble potato starch as previously described (15). One unit of amylase catalyzes the release of 1 jxmol reducing groups/min at 30°C in the presence of ...

Selenium: an insulin mimetic

“…Bosch et al [34] have found that vanadate inhibits the expression of transfected chimeras of PEPCK in both FTO-2B and H4IIE rat hepatoma cells. In adult rat hepatocytes in primary culture, vanadate in the presence of glucose induced L-type pyruvate kinase mRNA [35], and in a streptozocin-induced diabetic rat vanadate was found to increase pancreatic amylase mRNA [36]. In a similar light, oral administration of selenate to diabetic animals partly reversed abnormal liver expression of both glycogenic and gluconeogenic enzymes [37].…”