Altered anomeric specificity of glucose-induced insulin release in rabbits with duct-ligated pancreas.
Ligation of the pancreatic duct in rabbits provokes a decrease in the insulin and glucagon content of the pancreas, and may lead to chronic hyperglycemia. The insulin secretory behavior of the perfused pancreas is perturbed in duct-ligated animals, and this is illustrated in several respects: 1. The steady-state insulin output evoked by L-leucine (10 mM) is higher in duct-ligated than control rabbits; 2. In the presence of the amino acid, the response to D-glucose is characterized by a delayed onset, the absence of an early secretory peak, and a sluggish return towards basal value upon removal of the hexose from the perfusate; and 3. Whereas control rabbits display a higher secretory response to alpha- than beta-D-glucose, such is no more the case in duct-ligated rabbits. The perturbation of the anomeric specificity in secretory response is most obvious in diabetic duct-ligated rabbits, in which case beta-D-glucose stimulates insulin release more efficiently than alpha-D-glucose. In both control and duct-ligated rabbits, however, the alpha-anomer is more potent than the beta-anomer in suppressing leucine-stimulated glucagon secretion. These findings are compatible with the view that chronic hyperglycemia leads to alteration in the anomeric preference of the pancreatic B-cell for alpha-D-glucose, possibly as a result of the nonenzymatic glycation of glycolytic enzymes in insulin-producing, but not glucagon-producing, islet cells.
Fichaux
F
F
Laboratory of Experimental Medicine, Brussels Free University, Belgium.
Marchand
J
J
Yaylali
B
B
Leclercq-Meyer
V
V
Catala
J
J
Malaisse
W J
WJ
D000818:Animals; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000737:chemistry / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007930:Leucine / Q000494:pharmacology; D008026:Ligation; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010183:Pancreatic Ducts; D011817:Rabbits; D013237:Stereoisomerism
D007328:Insulin; D005934:Glucagon; D007930:Leucine; D005947:Glucose