Beneficial effects of sub-chronic activation of glucagon-like peptide-1 (GLP-1) receptors on deterioration of glucose homeostasis and insulin secretion in aging mice.
Aging is associated with an increased incidence of glucose intolerance and type 2 diabetes. Glucagon-like peptide-1 (GLP-1) is an important insulinotropic peptide secreted from the gastrointestinal tract in response to nutrient absorption. The present study was designed to assess the sub-chronic glucose regulatory effects of the potent long-acting GLP-1 receptor agonist, (Val(8))GLP-1, in aging 45-49 week old mice. Daily injection of (Val(8))GLP-1 (25 n mol/kg body weight) for 12 days had no significant effect on food intake, body weight, non-fasting plasma glucose and insulin concentrations. However, after 12 days, the glycaemic response to intraperitoneal glucose was improved (P<0.05) in (Val(8))GLP-1 treated mice. In keeping with this, glucose-mediated insulin secretion was enhanced (P<0.05) and insulin sensitivity improved (P<0.05) compared to controls. These data indicate that sub-chronic activation of the GLP-1 receptor by daily treatment with (Val(8))GLP-1 counters aspects of the age-related impairment of pancreatic beta-cell function and insulin sensitivity.
Irwin
Nigel
N
School of Biomedical Sciences, University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK. n.irwin@ulster.ac.uk <n.irwin@ulster.ac.uk>
McClean
Paula L
PL
Harriott
Patrick
P
Flatt
Peter R
PR
D000375:Aging / Q000502:physiology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000502:physiology; D004435:Eating / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006706:Homeostasis / Q000502:physiology*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D008297:Male; D051379:Mice; D010179:Pancreas / Q000378:metabolism; D018027:Receptors, Glucagon / Q000008:administration & dosage / Q000378:metabolism*
D001786:Blood Glucose; C000593834:Glp1r protein, mouse; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005947:Glucose