Impaired insulin secretion in the spontaneous diabetes rats.

Abstract

Dynamics of insulin and glucagon secretion were investigated by using a new model of spontaneous diabetes rats produced by the repetition of selective breeding in our laboratories. The perfusion experiments of the pancreas showed that the early phase of insulin secretion to continuous stimulation with glucose was specifically impaired, although the response of the early phase to arginine was preserved. The glucose-induced insulin secretion in the nineth generation (F8) which had a more remarkably impaired glucose tolerance was more reduced than in the sixth generation (F5). No significant difference of glucagon secretion in response to arginine or norepinephrine was noted between the diabetes rats and control ones. The present data indicate that the defective insulin secretion is a primary derangement in a diabetic state of the spontaneous diabetes rat. This defect in the early phase of glucose-induced insulin secretion suggests the specific impairment of the recognition of glucose by the pancreatic beta-cells. The spontaneous diabetes rats are very useful as a model of disease for investigating pathophysiology of non-insulin dependent diabetes mellitus.

Pulmonary Tuberculosis in Spontaneously Diabetic Goto Kakizaki Rats

“…Urinary glucose levels were (+) to (+++) in the GK/Jcl rats used. Impaired insulin secretion has been reported in GK/Jcl diabetic rats (Kimura et al 1982). Impaired glucose tolerance may be associated with active tuberculosis.…”

“…The defect in the early phase of glucose-induced insulin secretion suggests specific impairment of the recognition of glucose by pancreatic β -cells (Kimura et al 1982). There have been no previous reports on the development of tuberculosis in Goto Kakizaki diabetic rats.…”

Lack of compensatory increase in islet blood flow and islet mass in GK rats following 60% partial pancreatectomy

“…The GK (Goto-Kakizaki) rat is a non-obese animal model of hereditary non-insulin-dependent diabetes mellitus with mild hyperglycemia, initially derived from normal Wistar rats by repeatedly selecting animals with slightly aberrant glucose-tolerance tests for breeding (Goto & Kakizaki 1981, Kimura et al 1982, Suzuki & Goto 1987. The exact mechanism behind the impaired glucose-induced insulin release in the GK rat is unclear.…”

Pancreatic Function of Spontaneously Diabetic Torii Rats in Pre-Diabetic Stage

“…The GK rat is an animal model which exhibits hepatic insulin resistance in addition to functional and morphological changes in the pancreas, without obesity. In isolated islets of GK rats, GSIS is significantly decreased; thus, the first phase of GSIS is suppressed [7]. On the other hand, since the insulin secretory response to non-glucose (e.g., arginine, glibenclamide, a-ketoisocaproic acid) stimulation is well preserved in GK rats [15], the impaired glucose tolerance of GK rats is considered to be the primary cause of impaired insulin secretion in response to glucose stimulation in pancreatic b cells.…”

“…At present, Zucker Fatty (ZF) rats [23], Zucker Diabetic Fatty (ZDF) rats [26], Goto-Kakizaki (GK) rats [7], Otsuka Long-Evans Tokushima Fatty (OLETF) rats [5], etc. are widely employed as rat models of type 2 diabetes mellitus in order to analyze the onset of the disease and to develop antidiabetic agents.…”