Glucagon, insulin and somatostatin secretion in response to sympathetic neural activation in streptozotocin-induced diabetic rats. A study with the isolated perfused rat pancreas in vitro

Abstract

Summary. Changes in glucagon, insulin and somatostatin secretion induced by electrical splanchnic nerve stimulation were examined in rats treated with streptozotocin as neonates and as adults. In order to study the direct neural effects we used the isolated perfused rat pancreas with intact left splanchnic nerve in vitro. In normal rats splanchnic nerve stimulation causes significant decreases in insulin (30-40%) and somatostatin (30-50%) secretion at both 16.7 mmol/1 and 1 mmol/1 glucose concentrations. In the neonatal streptozotocin-diabetic rats splanchnic nerve stimulation at 16.7 mmol/1 glucose decreased insulin secretion (14%) further than in the control rats (30%), however, somatostatin secretion did not decrease to the same extent. Similar results were also observed at the low (1 mmol/1) glucose concentration. On the other hand, percent decreases of insulin and somatostatin secretion induced by splanchnic nerve stimulation in the streptozotocin-diabetic rats were similar to the values observed in the normal control rats. The glucagon secretion in response to splanchnic nerve stimulation at 16.7mmoi/I glucose from pancreatic Alpha ceils in both types of induced diabetes is exaggerated, and the degree of exaggeration seems to parallel the severity of the hyperglycaemia. However, the splanchnic nerve stimulation-induced glucagon secretion at 1 mmol/1 glucose was impaired in the streptozotocin-diabetic rats, but not in the neonatal streptozotocin-diabetic rats. These data suggest that the sensitivity of diabetic Alpha and Delta cells to sympathetic neural activation are blunted, whereas the sensitivity of Beta cells is enhanced in the diabetic animal model. Key words:Glucagon, insulin, somatostatin, streptozotocin, sympathetic nerve, diabetic rat.It has been reported that various clinical stress states are associated with catecholamine excess and hyperglycaemia, resulting in impaired insulin secretion and hyperglucagonaemia [1,2]. Furthermore, exaggerated glucagon responses to epinephrine have been observed in diabetic patients [2], and this exaggeration of glucagon secretion may have clinical importance in the pathogenesis of diabetes mellitus [3]. On the other hand, pancreatic Alpha-cell responses to changes in glucose concentrations are also abnormal in diabetes [4].Portha et al. [5] and Weir et al. [6] have reported independently that rats receiving streptozotocin during the neonatal period show a resemblance to human Type 2 (non-insulin-dependent) diabetes with a mild diabetic state showing selective insensitivity to glucose in Beta cells, while insulin secretion in response to other secretagogues is preserved. Furthermore, adult rats receiving streptozotocin develop severe insulin deficiency, and are considered to be one of the models of Type 1 (insulin-dependent) diabetes [7].In the present study we have investigated the effect of sympathetic neural activation on the endocrine pancreas in the animal models of diabetes. Furthermore, in order to elucidate the mechanism of abnormal glucagon secretion fro...

Impaired glucagon response to sympathetic nerve stimulation in the BB diabetic rat: effect of early sympathetic islet neuropathy

“…Two of the five doses of 6-OHDA produced degrees of islet sympathetic nerve terminal loss that bracketed the 65% loss seen in BB D. Importantly, the corresponding glucagon impairments during SNS of these two groups also bracketed the 57% impairment seen in BB D. Thus we conclude that the glucagon impairment during SNS in BB D is due to their islet nerve terminal loss and that the ␤-cell loss and hyperglycemia present in BB D had little additional effect. Previous data are consistent with this conclusion, as streptozotocin diabetes, which leaves islet nerve terminals intact, does not lead to an early impairment of the glucagon response to SNS in the isolated pancreas perfused with high glucose (28). We hypothesized that spontaneous islet nerve terminal destruction in BB D impaired the glucagon response to SNS by decreasing neurotransmitter release at the ␣-cell.…”

“…However, clinically significant DAN takes months to develop in rodents (28,30) and years to decades in humans (24). Because the glucagon response to insulin-induced hypoglycemia in the BB rat is severely impaired far earlier than the development of DAN (7), we considered it unlikely that DAN was the mediator of this specific, early glucagon impairment.…”

Leptin induces fasting hypoglycaemia in a mouse model of diabetes through the depletion of glycerol

“…4b), consistent with p r e v i o u s r e p o r t s [ 2 ] . I n r e s p o n s e t o f a s t i n g , hyperglucagonaemia was diminished in STZ-vehicle mice, potentially indicative of an impaired stimulated-glucagon response as has been shown for STZ-diabetic animals [17,18], whereas STZ-leptin mice had a non-significant trend towards increased glucagon levels compared with non-fasted levels. As corticosterone is implicated in the glucose-lowering action Time post pump (days) Fig.…”

Parasympathetic and sympathetic control of the pancreas: A role for the suprachiasmatic nucleus and other hypothalamic centers that are involved in the regulation of food intake

“…On the other hand, it reveals a close interaction between the parasympathetic and sympathetic motor nuclei, which may provide, in addition to the regulatory mechanisms at the level of the pancreas (Ahren and Taborsky, 1986;Kurose et al, 1992), the anatomic basis at the level of the CNS for the frequently observed cosecretion of insulin and glucagon (Steffens and Strubbe, 1983;Secchi et al, 1995;Taborsky et al, 1998).…”