Abnormal regulation of cAMP accumulation in pancreatic islets of obese mice.
The present study was undertaken 1) to determine whether a defect in the regulation of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was present in the beta-cell of the ob/ob mouse, 2) to determine how such a defect, if present, would alter the regulation of insulin secretion in these islets, and 3) to find out if epinephrine had similar effects on insulin secretion and cAMP production in islets of lean and obese mice. In the obese mouse, inhibitory modulators neither inhibited cAMP accumulation in intact islets nor adenylate cyclase activity in islet homogenates. These anomalies in the modulation of cAMP accumulation were not correlated with a failure to inhibit insulin secretion. It is concluded that, first, a defect in cAMP modulation is present in the islets of Langerhans of the obese mouse; second, epinephrine produces its effects on insulin secretion and cAMP accumulation via distinct mediators; and third, an anomaly in the adenylate cyclase system is unlikely to be the cause of the exaggerated insulin secretion in the islet of the ob/ob mouse. It is more likely that the exaggerated insulin secretion is due to a faulty cation gating mechanism that, in turn, may contribute to the impaired ability of the islet to accumulate cAMP.
Black
M A
MA
Department of Biochemistry, University of Ottawa, Canada.
Heick
H M
HM
Bégin-Heick
N
N
D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C / Q000378:metabolism; D008820:Mice, Obese / Q000378:metabolism*; D012016:Reference Values; D013045:Species Specificity; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D007328:Insulin; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D000262:Adenylyl Cyclases