Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Mediating Insulin Secretion in Rodent Pancreatic Islets Are Coupled to Adenylate Cyclase But Not to PLC

Inosine is a potent primary stimulus of insulin secretion from isolated mouse islets. The inosine-induced insulin secretion was totally depressed during starvation, but was completely restored by the addition of 5 mM-caffeine to the medium and partially restored by the addition of 5 mM-glucose. Mannoheptulose (3 mg/ml) potentiated the effect of 10 mM-inosine in islets from fed mice. The mechanism of the stimulatory effect of inosine was further investigated, and it was demonstrated that pancreatic islets contain a nucleoside phosphorylase capable of converting inosine into hypoxanthine and ribose 1-phosphate. Inosine at 10 mM concentration increased the lactate production and the content of ATP, glucose 6-phosphate (fructose 1,6-diphosphate + triose phosphates) and cyclic AMP in islets from fed mice. In islets from starved mice inosine-induced lactate production was decreased and no change in the concentration of cyclic AMP could be demonstrated, whereas the concentration of ATP and glucose 6-phosphate rose. Inosine (10 mM) induced a higher concentration of (fructose 1,6-diphosphate + triose phosphates) in islets from starved mice than in islets from fed mice suggesting that in starvation the activities of glyceraldehyde 3-phosphate dehydrogenase or other enzymes below this step in glycolysis are decreased. Formation of glucose from inosine was negligible. Inosine had no direct effect on adenylate cyclase activity in islet homogenates. The observed changes in insulin secretion and islet metabolism mimic what is seen when glucose and glyceraldehyde stimulate insulin secretion, and as neither ribose nor hypoxanthine-stimulated insulin release, the results are interpreted as supporting the substrate-site hypothesis for glucose-induced insulin secretion according to which glucose has to be metabolized in the beta-cells before secretion is initiated.

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Inhibition of Dipeptidyl Peptidase-4 Augments Insulin Secretion in Response to Exogenously Administered Glucagon-Like Peptide-1, Glucose-Dependent Insulinotropic Polypeptide, Pituitary Adenylate Cyclase-Activating Polypeptide, and Gastrin-Releasing Peptide in Mice

Endocrinology ◽

10.1210/en.2004-1174 ◽

2005 ◽

Vol 146 (4) ◽

pp. 2055-2059 ◽

Cited By ~ 64

Author(s):

Bo Ahrén ◽

Thomas E. Hughes

Keyword(s):

Insulin Secretion ◽

Adenylate Cyclase ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase 4 ◽

Gastrin Releasing Peptide ◽

Pituitary Adenylate Cyclase ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

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A new recombinant pituitary adenylate cyclase-activating peptide-derived peptide efficiently promotes glucose uptake and glucose-dependent insulin secretion

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gms078 ◽

2012 ◽

Vol 44 (11) ◽

pp. 948-956 ◽

Cited By ~ 2

Author(s):

Y. Ma ◽

T. Luo ◽

W. Xu ◽

Z. Ye ◽

A. Hong

Keyword(s):

Insulin Secretion ◽

Adenylate Cyclase ◽

Glucose Uptake ◽

Pituitary Adenylate Cyclase

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A 67 kDa protein mediates pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal peptide-stimulated insulin secretion in a hamster clonal β-cell line

Journal of Endocrinology ◽

10.1677/joe.0.1470121 ◽

1995 ◽

Vol 147 (1) ◽

pp. 121-130 ◽

Cited By ~ 10

Author(s):

R N Kulkarni ◽

D M Smith ◽

M A Ghatei ◽

S R Bloom

Keyword(s):

Insulin Secretion ◽

Adenylate Cyclase ◽

Cell Line ◽

Vasoactive Intestinal Peptide ◽

Binding Studies ◽

Β Cell ◽

Islet Amyloid ◽

Amino Acid Peptide ◽

Pituitary Adenylate Cyclase ◽

Chemical Cross Linking

Abstract Insulin secretion is regulated by neural and neurohormonal factors. The report of nerves releasing pituitary adenylate cyclase-activating polypeptide (PACAP) – a 38 amino acid peptide – in the endocrine pancreas, suggests it may be important in modulating insulin release. We therefore carried out receptor-binding studies on membranes prepared from the glucose-responsive clonal β-cell line HIT-T15, and also examined the effects of PACAP38, PACAP27 – a C-terminal truncated form of the peptide – and vasoactive intestinal peptide (VIP) on insulin and islet amyloid polypeptide (IAPP) release. We showed by chemical cross-linking that PACAP and VIP stimulate secretion from the clonal cells by binding to a receptor with a molecular weight of 67 kDa (n=4). Binding was saturable when membranes were incubated with 125I-PACAP27 (Kd 1·2±0·2 nm; Bmax 415·7±35·3 fmol/mg; n=4) or 125I-VIP (Kd 1·3±0·3 nm; Bmax 354·8 ± 42·8 fmol/mg; n=4). We also demonstrated an increase in glucose-stimulated insulin (PACAP27, 366·6 ±25·8% PACAP38, 389·9 ±13·4%; VIP, 342·6± 16·1% of control; all at 1 μm, P<0·01 vs control) and IAPP release (PACAP27, 236·9 ±26·2%; PACAP38, 226·5 ± 10·9%; VIP, 242·9 ± 15·8% of control; all at 1 μm, P<0·01 vs control). Incubation of the cells with these peptides, for a duration of 12 h, in the presence of 5·5 mm glucose, did not alter the expression of insulin or IAPP. These findings suggest that PACAP and VIP stimulate secretion of insulin and IAPP by binding to a 67 kDa protein on clonal β-cells and do not alter the transcription of insulin and IAPP under the conditions tested. Journal of Endocrinology (1995) 147, 121–130

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