Reversal of D- and A-cell insensitivity to glucose in alloxan-diabetic dogs by treatment with the artificial beta cell (Biostator).
Insulin-deficient diabetes in man as well as in experimental diabetes is associated with islet cell insensitivity to glucose. The present study was designed to determine whether this abnormality could be counteracted either by increasing the intraislet insulin level or by normalizing the diabetic state by a glucose-controlled insulin infusion system (GCIIS: Biostator, Life Science Instruments, Elkhart, Indiana). Using the isolated, perfused pancreas of dogs with moderate, untreated alloxan diabetes of 4 days duration, we found that 5 mM arginine (N = 4) and 5 mM calcium (N = 4) stimulated D- and A-cell secretion, whereas an increment in glucose from 1.3 to 11 mM (N = 4) had no effect on islet hormone secretion. In the pancreas from untreated alloxan-diabetic dogs, acute infusion of large amounts of insulin (25 mU/ml) in vitro simultaneously with an elevation of perfusate glucose from 1.3 to 11 mM failed to restore the glucose from 1.3 to 11 mM failed to restore the glucose sensitivity. In contrast, treatment of alloxan-diabetic dogs (N = 3) by a GCIIS for 24 h revived some responsiveness of the glucagon, insulin, and somatostatin to glucose (1.3-11 mM) of the subsequently perfused pancreas. It is concluded that the insensitivity to glucose of islet cells in insulin-deficient diabetes is not ascribed to an intra-islet insulin deficiency per se but rather to an abnormal metabolic state secondary to insulin deficiency. The results also indicate that the glucose receptor dysfunction is not due to a direct lesion by the diabetogenic drug.
Hermansen
K
K
Schmitz
O
O
Orskov
H
H
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004285:Dogs; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007332:Insulin Infusion Systems; D007515:Islets of Langerhans / Q000187:drug effects; D013004:Somatostatin / Q000097:blood
D001786:Blood Glucose; D007328:Insulin; D013004:Somatostatin; D005934:Glucagon; D001120:Arginine; D005947:Glucose