Contribution of neural intrapancreatic non-cholinergic non-adrenergic mechanisms to glucose-induced insulin release in the isolated rat pancreas

Abstract

In the isolated rat pancreas the effect of intrapancreatic non-adrenergic non-cholinergic nerves was examined upon insulin, glucagon and somatostatin release during perturbations of perfusate glucose. Elevation of glucose from 1.6 to 8.3 mmol/l increased insulin and somatostatin secretion and inhibited glucagon release. The first phase of insulin secretion was significantly reduced by the neurotoxin tetrodotoxin to 55% of the controls (p < 0.05). The somatostatin response was attenuated by tetrodotoxin while the change of glucagon remained unaffected. In contrast the combined adrenergic and cholinergic blockade with atropine, phentolamine and propranolol (10(-5) mol/l) did not modify the insulin, glucagon and somatostatin response. When glucose was changed from 8.3 to 1.6 mmol/l, the reduction of insulin and somatostatin release was not modified by tetrodotoxin, but stimulation of glucagon was significantly attenuated by 60-70% (p < 0.03), which was similar to the effect of combined adrenergic and cholinergic blockade. Subsequently, the effect of neural blockade was examined during more physiological perturbations of perfusate glucose levels. When glucose was changed from 3.9 to 7.2 mmol/l, tetrodotoxin also attenuated first phase insulin response by 40% while cholinergic and adrenergic blockade had no effect. The nitric oxide synthase inhibitor NG-Nitro-L-arginine-methyl-ester (L-NAME) did not alter the glucose-induced insulin response indicating that nitric oxide is not involved in this mechanism. It is concluded that neural non-adrenergic non-cholinergic mechanisms contribute to the first, but not second phase of glucose-induced insulin release. Non-adrenergic non-cholinergic effects do not participate in regulation of glucagon and somatostatin secretion under the conditions employed.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of obesity and insulin resistance by nitric oxide

“…However, NO is suggested to stimulate islet cell insulin secretion by inducing calcium release from mitochondria [315], which may be due to NO-mediated inhibition of respiration and mitochondrial depolarization. Nevertheless, the stimulatory effects of NO on insulin secretion are relatively subtle [314], which might explain why other studies suggest that NO is not involved in the initiation of insulin secretion from pancreatic islets [316, 317]. …”

Does Nitric Oxide Play Role in Stimulus–Secretion and/or Synthesis–Secretion Coupling of Insulin?

“…There are conflicting reports of NO increasing insulin release, as well as decreasing insulin release (12)(13)(14)(15)(16). In addition, some investigators claimed that NO is involved neither in the initiation of insulin release, nor in insulin release induced by cationic amino acids such as arginine (17)(18)(19)(20). In this study we examined the possible role of NO in argininemediated insulin release, especially the differential effects of this amino acid on first-phase and second-phase glucose-stimulated insulin release, by using the perfused rat pancreas model.…”

The anti-obesogenic effects of nitric oxide.

“…NO has been suggested to stimulate islet cell insulin secretion by inducing calcium release from mitochondria 527 , which may be due to NO-mediated inhibition of respiration and mitochondrial depolarization. Nevertheless, the stimulatory effects of NO on insulin secretion are relatively subtle 526 , which might explain why some studies suggest that NO is not involved in the initiation of insulin secretion from pancreatic islets 528,529 .…”