Responses of the pancreatic A cell during hypoglycemia and hyperglycemia are dependent on the B cell.
It is controversial whether stimulation of glucagon secretion by hypoglycemia or suppression by hyperglycemia is a direct effect of glucose on the A cell or whether it is mediated indirectly through the B cell. To determine the role of the B cell in the mediation of glucagon secretion adolescent male baboons were studied before and after successive injections of streptozocin designed to cause B-cell destruction in a series of stages. Following one dose of streptozocin, B-cell function was impaired but fasting blood glucose remained normal. B-cell function declined further with additional doses of streptozocin. As B-cell function declined, there was a corresponding reduction in the glucagon response to hypoglycemia (Ghyp). There were significant correlations between the percentage reduction in Ghyp and the percentage reduction in B-cell function (acute insulin response to arginine, r = .47; acute insulin response to glucose, r = .69; Kg, r = .79). In a second study the ability of hyperglycemia to suppress the acute glucagon response to arginine (AGRarg) was studied. Before streptozocin AGRarg was 128 +/- 26 pg/mL at a glucose level of 80 +/- 4 mg/dL and was suppressed to 74 +/- 20 pg/mL when glucose was raised and clamped at 209 +/- 14 mg/dL. After the initial dose of streptozocin, with mild B cell damage and fasting normoglycemia, AGRarg was not suppressed by hyperglycemia. With severe B cell dysfunction and fasting hyperglycemia, there was paradoxical enhancement of AGRarg by additional hyperglycemia. In conclusion, the ability of the A cell to respond appropriately to hypoglycemia and to arginine during hyperglycemia is dependent on normal B-cell function.
McCulloch
D K
DK
Department of Medicine, Pacific Medical Center, Seattle.
Raghu
P K
PK
Koerker
D J
DJ
Palmer
J P
JP
Klaff
L J
LJ
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D005934:Glucagon / Q000097:blood / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000503:physiopathology*; D007003:Hypoglycemia / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D010179:Pancreas / Q000503:physiopathology*; D010215:Papio
D007328:Insulin; D005934:Glucagon; D001120:Arginine; D005947:Glucose