Release of Catecholamines Is Increased but Does Not Contribute to the Impaired Insulin Secretion in the Perfused Pancreata of Diabetic Rats

Abstract

Insulin response to glucose is severely impaired in patients with non-insulin-dependent diabetes mellitus (NIDDM). Also in a rat model of NIDDM, neonatally streptozotocin diabetic rats (STZ), the insulin response to glucose is profoundly suppressed when studied in vivo or in the perfused pancreas. The insulin response was better preserved from isolated islets obtained from patients and STZ rats. Since alpha 2-adrenoceptor stimulation suppresses insulin secretion, catecholamines from intrapancreatic nerve terminals may be involved in the mechanism behind the marked impairment of the glucose-stimulated insulin response in the intact pancreas. We have studied the pancreatic content and release--or overflow--of catecholamines from the isolated, perfused pancreas of STZ rats. The overflow of noradrenaline (NA) in the perfusate was two- to threefold higher in pancreata from STZ than from nondiabetic rats, and perfusion with a high glucose concentration increased the NA overflow in both types of pancreata. Levels of adrenaline (ADR) were always low in perfusates of nondiabetic glands, but increased in five of seven perfusions of STZ glands. The pancreatic contents of NA and ADR were similar in STZ and nondiabetic rats. Pretreatment of rats with reserpine 24 h before perfusions reduced the pancreatic content of NA and ADR by > 90% in both STZ and nondiabetic rats. Reserpine also diminished the overflow of NA in the perfusate from STZ rats by > 90% and from nondiabetic rats by 58-77%. After reserpine, however, glucose-induced insulin release was not enhanced in either STZ or control pancreata. In conclusion, overflow of catecholamines is higher in the pancreas of STZ than of nondiabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)