Beta-cell tropin- and glucose-induced hypersecretion of insulin and amylin from perfused fatty rat pancreas.
The neurointermediate pituitary peptide beta-cell tropin (BCT) has potent insulin-releasing and lipogenic properties and is elevated in obesity and type-2 diabetes. The effects of BCT and glucose on the release of insulin and amylin from the perfused pancreas of obese 'fatty' (fa/fa) rats and lean (Fa/?) controls were measured. Pancreata were perfused, sequentially, with buffer containing: 5.6 mmol glucose/l (basal); basal glucose +/- 0.5 nmol BCT/l; 16.7 mmol glucose/l (high). Insulin and amylin release during basal glucose treatment was eight to nine times greater from pancreata from fatty than from lean rats. BCT induced a fivefold greater monophasic insulin and amylin release from fatty compared with lean pancreata. When not preceded by BCT there was a twofold greater high glucose-induced amylin release from fatty pancreata but no difference in insulin secretion. When preceded by BCT stimulation, high glucose induced twofold greater insulin and fourfold larger amylin release from fatty compared with lean pancreata. Molar secretion ratios of insulin:amylin varied between 30:1 and 50:1. In view of the elevated levels of BCT found in the fatty rat and in the light of the above findings, it is concluded that the peptide may have a role in the development of hyperinsulinaemia, hyperamylinaemia and insulin resistance in this animal model of obesity and diabetes.
Clore Laboratory for Life Sciences, University of Buckingham, U.K.
S J
SJ
Dunmore
M A
MA
Cawthorne
D C
DC
Hislop
J L
JL
Morton
A
A
Beloff-Chain
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D009924:Organ Culture Techniques; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D011924:Rats, Zucker; D013268:Stimulation, Chemical
D000682:Amyloid; D007328:Insulin; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C026834:beta-cell tropin; D000324:Adrenocorticotropic Hormone; D005947:Glucose