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Release of insulin and glucagon from perfused pancreases in vitro of 40 normal male and female Chinese hamsters (from one inbred subline) and 110 male and female diabetic hamsters (from three inbred sublines) was measured in response to glucose plus arginine, theophylline alone, or potassium alone, in order to determine if differences in hormone secretion exist among different diabetic sublines. Glucose plus arginine and potassium produced subnormal insulin responses in all three diabetic sublines, whereas theophylline induced 'normal' or above normal insulin responses. Excessive glucagon release was consistently seen in only one diabetic subline. The female normal animals showed greater insulin release than the male normal hamsters in response to glucose plus arginine. This sex difference was not seen in the diabetic animals.

Hereditary insulin-deficient diabetes mellitus occurs in certain sublines of nonobese Chinese hamsters. Several characteristics of this syndrome are similar to those seen in insulin-deficient human diabetics. Therefore, to characterize pancreatic islet function, dynamic insulin and glucagon release from normal and nonketotic diabetic hamster pancreases in response to glucose (300 mg/100 ml) and theophylline (10 mM), infused singly and together, was studied in vitro.20-min glucose infusions of normal hamster pancreases caused biphasic insulin release, consisting of a rapid first peak and a gradually rising second phase, similar to that reported for man in vivo. Both phases were significantly reduced in the diabetic pancreases. Theophylline alone stimulated similar nonphasic insulin release in both the normal and the diabetic pancreases. Glucose and theophylline together caused greater insulin release than either stimulant alone in both normals and diabetics; however, the diabetic response was still subnormal. Glucose suppressed glucagon release from normal pancreases; suppression was significantly impaired in diabetics. Theophylline stimulated nonphasic glucagon release in both the normals and diabetics. Glucose partially suppressed the theophylline-stimulated release in both groups.Insulin/glucagon molar ratios of the diabetics were consistently subnormal, although individual hormone levels often overlapped into the normal range. IN SUMMARY, THE PANCREASES OF GENETICALLY DIABETIC CHINESE HAMSTERS PERFUSED IN VITRO SHOWED: (a) decreased first and second phase insulin release in response to glucose-containing stimuli-only partially ameliorated by theophylline-, and (b) impaired suppression of glucagon in response to glucose, resulting in (c) a decreased insulin/glucagon molar ratio. These data support the suggestion that both alpha and beta cells of diabetic pancreases may be insensitive to glucose.

Nonketotic, genetically diabetic Cinese hamsters show subnormal pancreatic insulin release and impaired suppression of glucagon in response to glucose. To study the pancreatic effects of other agents, dynamic insulin and glucagon release was measured from the in vitro perfused pancreases of normal and diabetic Chinese hamsters in response to various combinations of arginine (20mM), glucose (100 or 150 mg. per 100 ml.), and theophylline (10 mM). Theophylline alone caused identical insulin and glucagon release in diabetics and normals. Glucose, alone and in the presence of theophylline, caused subnormal insulin release and less suppression of glucagon release in the diabectics than in the normals. Arginine, in the presence of glucose and theophylline, caused excessive glucagon release but nearly normal insulin release in the diabetics. Arginine, in the absence of glucose or theophylline, caused excessive glucagon release in the diabetics and undetectable insulin release in either diabetics or normals. Pancreatic content after perfusion did not correlate with release during perfusion. Infusion of arginine alone markedly decreased the amount of extractable pancreatic insulin and glucagon. These results indicate that the pancreatic alpha cell of the diabetic Chinese hamster responds excessively to arginine, as is seen in the human diabetic. This defect is not related to acute insulin release or the presence of glucose. Further, these results confirm that the diabetic Chinese hamster's alpha and beta cells respond normally to theophylline, but are relatively insensitive to glucose.

Rat pancreases were perfused in vitro for 5-min periods with K+ alone (8, 10, and 12 mM) or in the presence of arginine (10 mM). Alone, K+ caused bursts of insulin, glucagon, and somatostatin (SRIF) release; with arginine, it caused a burst of insulin and sustained SRIF release, but caused sustained suppression of glucagon. This suppression correlated better with SRIF than insulin release. Therefore, if a paracrine effect is responsible for the inhibition of glucagon secretion under these circumstances, SRIF is a more likely candidate than insulin.

Diabetes mellitus spontaneously develops in certain sublines of non-obese Chinese hamsters, and the diabetic L-subline is known for subnormal pancreatic insulin release in vitro. The cause of the secretory defect is unknown. Freeze-dried pancreas sections from genetically diabetic Chinese hamsters and normal controls were subjected to proton bombardment and the concentration of 15 elements in B cells and acini was calculated from the X-rays emitted. Diabetic B cells contained significantly less Al (-61%) and significantly more Cu (+92%), Mg (+6%) and Rb (+13%) than their normal counterparts. The diabetic acini showed similar, significant changes. The molar ratio between K and Na was about 10 in endocrine as well as exocrine pancreas from both groups of animals, implying that neither sample preparation nor irradiation had induced significant diffusive changes. In conclusion, the high K/Na ratio suggests that the diabetic B cell has a well-functioning Na+/K+ pump. However, significant and parallel changes in Al-, Cu-, Mg- and Rb-levels were found in both the B cells and acinar portion of the diabetic pancreas. It is not clear whether these elemental changes cause the islet secretory defect or result from it.