The effect of ventromedial hypothalamic nuclei destruction on somatostatin and insulin release from the isolated perfused rat pancreas (original) (raw)

Glucose stimulation of somatostatin and insulin release from the isolated, perfused rat pancreas

Diabetes, 1980

Insulin and somatostatin release from the isolated perfused rat pancreas was studied under conditions of 50 and 300 mg/dl glucose as well as a linear 50-300 mg/dl glucose gradient. The glucose-stimulated response profile of somatostatin was nearly parallel to that of insulin in both the acute and gradient dose experiments. Antisomatostatin serum was without significant effect on glucose-stimulated insulin release. In spite of the marked, fifteenfold stimulation of somatostatin release (1.5 x 10 10 M in the perfusate effluent) by glucose, the concentration of somatostatin was insufficient to significantly alter glucose-stimulated insulin release in the isolated perfused rat pancreas. DIABETES 29:747-751, September 1980.

Somatostatin inhibits pancreatic exocrine secretion via a neural mechanism

Metabolism, 1990

The mechanism of inhibition of pancreatic exocrine secretion by somatostatin is unknown. We hypothesized that somatostatin acts indirectly, via intrinsic pancreatic neurons, to inhibit pancreatic exocrine secretion. To test this hypothesis, amylase and volume outputs in response to secretin (1 O-* mol/L) and cholecystokinin octapeptide (CCK) (10-s mol/L) were studied in the rat isolated, perfused, pancreas model. Somatostatin (IO-' mol/L) significantly inhibited amylase output by 48% compared with control (352 + 57 v 878 + 85 U/30 min, P < .05 by ANOVA). Blockade of axonal neuronal transmission by tetrodotoxin (lo-' mol/L) completely abolished the inhibitory effect of somatostatin (992 * 53 U/30 mitt). Similar effects were seen on volume output. The inhibitory effect of somatostatin on amylase output was not affected by cholinergic receptor blockade with atropine (328 + 85 U/30 min) or by sympathetic ganglionic blockade with hexamethonium (380 + 88 U/30 min). This suggests that the intrinsic pancreatic neurons responsible for the inhibitory effect of somatostatin are peptidergic. The possibility that somatostatin acts directly on the acinar cell to inhibit exocrine secretion was tested by incubating varying doses of somatostatin (1 O-l* to lo-' mol/L) with isolated pancreatic acini in the presence of graded concentrations of CCK (1 O-" to lo-" mol/L). In this model, CCK alone is a potent stimulant of amylase release, with a Km of 8 x 1 O-" mol/L and a V, of 22 + 3% total amylase. In this model, somatostatin had no inhibitory effect. The possibility that somatostatin releases a secondary inhibitory mediator from the pancreas was tested by perfusing rat pancreata arterially with 1 O-' mol/L somatostatin and collecting portal venous effluent. Aliquots of unconcentrated and SO-fold concentrated portal venous effluent were tested for inhibitory activity in the isolated acinar preparation in the presence of graded concentrations of CCK. As control, portal venous effluent was collected from pancreata perfused arterially with buffer alone. No inhibitory activity was identified in these perfusates suggesting that somatostatin does not release a secondary inhibitory substance to modulate pancreatic inhibition. We conclude that the mechanism of inhibition of pancreatic exocrine secretion by somatostatin is indirect, via intrinsic, inhibitory pancreatic neurons. These neurons are likely peptidergic.

Influence of the sympatho-adrenal system and somatostatin on the secretion of insulin in the rat

The Journal of physiology, 1981

1. The effects of somatostatin on insulin secretion in anaesthetized rats subjected to different manipulations of the sympatho-adrenal system have been investigated.2. Somatostatin (0.1 mug/min) inhibited the secretion of insulin in intact rats both in the basal state and after inducing an enhanced insulin release by infusion of the alpha-adrenoceptor-blocker phentolamine.3. Combined surgical splanchnicotomy and adrenalectomy caused an increase in the basal plasma insulin concentration. Somatostatin (0.1 mug/min) inhibited basal insulin release also in these rats. After infusion of phentolamine, however, the dose of somatostatin had to be raised five fold (0.5 mug/min) to achieve a comparable inhibition of insulin release. On the other hand, a similar rate of insulin secretion induced by glucose in intact rats could be inhibited by the lower dose of somatostatin.4. Administration of the beta-adrenoceptor-blocking agent propranolol to splanchnicotomized-adrenalectomized rats lowered ...

Influence of insulin in the ventromedial hypothalamus on pancreatic glucagon secretion in vivo

2010

OBJECTIVE-Insulin released by the ␤-cell is thought to act locally to regulate glucagon secretion. The possibility that insulin might also act centrally to modulate islet glucagon secretion has received little attention. RESEARCH DESIGN AND METHODS-Initially the counterregulatory response to identical hypoglycemia was compared during intravenous insulin and phloridzin infusion in awake chronically catheterized nondiabetic rats. To explore whether the disparate glucagon responses seen were in part due to changes in ventromedial hypothalamus (VMH) exposure to insulin, bilateral guide cannulas were inserted to the level of the VMH and 8 days later rats received a VMH microinjection of either 1) anti-insulin affibody, 2) control affibody, 3) artificial extracellular fluid, 4) insulin (50 U), 5) insulin receptor antagonist (S961), or 6) anti-insulin affibody plus a ␥-aminobutyric acid A (GABA A) receptor agonist muscimol, prior to a hypoglycemic clamp or under baseline conditions. RESULTS-As expected, insulin-induced hypoglycemia produced a threefold increase in plasma glucagon. However, the glucagon response was fourfold to fivefold greater when circulating insulin did not increase, despite equivalent hypoglycemia and C-peptide suppression. In contrast, epinephrine responses were not altered. The phloridzin-hypoglycemia induced glucagon increase was attenuated (40%) by VMH insulin microinjection. Conversely, local VMH blockade of insulin amplified glucagon twofold to threefold during insulin-induced hypoglycemia. Furthermore, local blockade of basal insulin levels or insulin receptors within the VMH caused an immediate twofold increase in fasting glucagon levels that was prevented by coinjection to the VMH of a GABA A receptor agonist. CONCLUSIONS-Together, these data suggest that insulin's inhibitory effect on ␣-cell glucagon release is in part mediated at the level of the VMH under both normoglycemic and hypoglycemic conditions.