The effects of islet activating protein on oral glucose tolerance in the genetically obese fa/fa rat.
When tested in insulin-deficient animal models of diabetes, islet activating protein (IAP) has been shown to increase the secretion of insulin and to improve glucose intolerance. The genetically obese fa/fa rat is an animal model of impaired oral glucose tolerance that does not have reduced insulin secretion. In this model IAP treatment increases basal insulin levels, resulting in lower basal glycemia. However, glucose tolerance following an oral glucose load was worsened by IAP. This was found to be due to an exaggerated stimulation of hepatic glucose production (HGP) following glucose, a defect that is already present in the absence of IAP. IAP has been reported to inhibit (by ADP ribosylation) the inhibitory regulatory protein (Ni) of adenylate cyclase. It is therefore suggested that the increased HGP following oral glucose in fa/fa rats either in the absence or in the presence of IAP treatment may result from a cAMP-mediated mechanism. A beta adrenergic activation or a stimulation of glucagon output could therefore be potential candidates responsible for glucose intolerance in obese fa/fa rats.
Proietto
J
J
Laboratoires de Recherches Métaboliques, University of Geneva, Switzerland.
Rohner-Jeanrenaud
F
F
Ionescu
E
E
Jeanrenaud
B
B
D037361:Adenylate Cyclase Toxin; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D007328:Insulin / Q000097:blood; D008099:Liver / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism*; D037342:Pertussis Toxin; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D037361:Adenylate Cyclase Toxin; D001786:Blood Glucose; D007328:Insulin; D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin; D005947:Glucose