GPR40 Is Necessary but Not Sufficient for Fatty Acid Stimulation of Insulin Secretion In Vivo

Abstract. The ability of the cholinergic agonist carbachol to sensitize islets to the action of combined glucose, cholecystokinin and gastric inhibitory polypeptide was determined in isolated rat islets. In response to this combination, peak first phase insulin secretion from control islets averages 85 ± 5 pg · islet−1 · min−1 (mean ± sem) and the insulin secretory rates measured 35–40 min after the onset of stimulation averages 127 ± 34 pg · islet−1 · min−1. A prior 20 min exposure to 1 mmol/l carbachol potentiates the modest insulin stimulatory response to this combination of stimulants: peak first phase release is 354 ± 61 pg · islet−1 · min−1, and release measured 35–40 min after the onset of stimulation is 179 ± 34 pg · islet−1 · min−1. This sensitizing effect of carbachol lasts for at least 40 min and can be duplicated by the natural in vivo agonist acetylcholine. These results demonstrate that cholinergic stimulation of isolated islets primes them to the subsequent stimulatory effect of a moderate increase in the circulating glucose level and to several postulated incretin factors. If operative in vivo, this communications network between cephalic and enteric factors represents a remarkable control system to ensure the release of insulin in amounts commensurate to meet the anticipated and actual insulin requirements for insulin-mediated fuel disposition.

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Disruption of GPR39 Impairs Insulin Secretion In Vivo

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.94.4.9998 ◽

2009 ◽

Vol 94 (4) ◽

pp. 1472-1472

Author(s):

Frédéric Tremblay ◽

Ann-Marie T. Richard ◽

Sarah Will ◽

Jameel Syed ◽

Nancy Stedman ◽

...

Keyword(s):

Insulin Secretion ◽

Insulin Secretion In Vivo

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Hyperinsulinemia of preobese and obese fa/fa rats is partly vagus nerve mediated

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1983.244.4.e317 ◽

1983 ◽

Vol 244 (4) ◽

pp. E317-E322 ◽

Cited By ~ 7

Author(s):

F. Rohner-Jeanrenaud ◽

A. C. Hochstrasser ◽

B. Jeanrenaud

Keyword(s):

Electrical Stimulation ◽

Insulin Secretion ◽

B Cells ◽

Vagus Nerve ◽

Zucker Rats ◽

Glucose Load ◽

Parasympathetic System ◽

Enhanced Sensitivity ◽

Stimulation Of

In vivo glucose-induced insulin secretion was greater in preweaned preobese 17-day-old Zucker rats than in the corresponding controls. This hypersecretion of insulin was reversed to normal by acute pretreatment with atropine. A short-lived (30 s) electrical stimulation of the vagus nerve preceding a glucose load potentiated the in vivo glucose-induced insulin release in adult animals (6-9 wk) and more so in obese Zucker (fa/fa) than in lean rats. This suggested the existence of enhanced sensitivity and/or responsiveness of the B cells of obese animals to the parasympathetic system. That the parasympathetic tone was increased in adult obese Zucker (fa/fa) rats was corroborated by the observation that acute vagotomy of these animals resulted in a significant decrease in glucose-induced insulin secretion, whereas no such effect was seen in lean rats. Also, perfused pancreases from adult obese (fa/fa) rats oversecreted insulin during a stimulation by arginine when compared with controls, an oversecretion that was restored toward normal by superimposed infusion of atropine. It is concluded that a) the increased insulin secretion of preobese Zucker fa/fa rats is an early abnormality that is mediated by the vagus nerve, and b) increased secretion of insulin in adult obese fa/fa rats continues to be partly vagus-nerve mediated, although a decreased sympathetic tone and other unknown defects could conceivably play a role as well.

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