Effects of growth hormone-releasing hormone on the secretion of islet hormones and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats.
The effect of synthetic human growth hormone-releasing hormone(1-40) (hGHRH-40) on the function of the endocrine pancreas and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats has been examined. The addition of 1 mumol hGHRH-40/1 to incubated islets from normal lean mice increased insulin release by 90 and 37% at 5.6 and 16.7 mmol glucose/l respectively. Lower concentrations of hGHRH-40 did not affect insulin release. hGHRH-40 (1 mumol/l) increased pancreatic polypeptide release by 50% at 5.6 mmol glucose/l. A range of concentrations of hGHRH-40 (1 nmol/l-1 mumol/l) reduced glucagon release by 42-73% at 5.6 mmol glucose/l, and by 38-70% at 16.7 mmol glucose/l. Somatostatin release was increased (eightfold) by 1 mumol hGHRH-40/1 at 5.6 mmol glucose/1, but at 1 nmol hGHRH-40/1 somatostatin release was reduced (by greater than 50%). At 16.7 mmol glucose/litre 0.01-1 mumol hGHRH-40/1 increased somatostatin release (three- to fourfold), but 1 nmol hGHRH-40/1 produced a reduction of 50%. In vivo, administration of hGHRH-40 (50 micrograms/kg body weight i.p.) to fasted lean and ob/ob mice did not alter basal plasma concentrations of glucose and insulin, or the glucose and insulin responses to a concomitant i.p. glucose challenge. Intravenous injection of hGHRH-40 (20 micrograms/kg body weight) to anaesthetized rats increased plasma concentrations of insulin in the hepatic portal vein. A lower dose of hGHRH-40 (0.2 micrograms/kg) was ineffective, and neither dose of hGHRH-40 altered plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)
Bailey
C J
CJ
Department of Pharmaceutical Sciences, Aston University, Birmingham.
Wilkes
L C
LC
Flatt
P R
PR
Conlon
J M
JM
Buchanan
K D
KD
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005934:Glucagon / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008820:Mice, Obese; D010191:Pancreatic Polypeptide / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012636:Secretory Rate / Q000187:drug effects; D013004:Somatostatin / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D010191:Pancreatic Polypeptide; D005934:Glucagon; D013007:Growth Hormone-Releasing Hormone