DIMA Replication in Pancreatic Islets and Adrenals in Diabetic Chinese Hamsters

Abstract

The diabetic syndrome in Chinese hamsters is progressive and there is a decrease in the size of the pancreatic islets. To what extent this is due to impaired DNA replication in their islet cells is unknown. Therefore ³H-thymidine incorporation into islet cells was studied in genetically diabetic (subline L) male hamsters aged 17-20 days, 6 weeks, 3, 6 and 12 months. Because adrenal weight was decreased at almost all ages, studies of adrenal morphology and function were also performed. Age- and sex-matched normal (subline M) hamsters served as controls. Autoradiography showed progressively falling labeling with increasing age in both normal and diabetic animals in both islets and adrenals. At the earliest age studied, the diabetic subline animals were normoglycemic but showed hyperinsulinemia. DNA replication was reduced both in the islet cells and the adrenal cortex. From 6 weeks of age and onwards, the diabetic hamsters were hyperglycemic and usually hyperinsulinemic but DNA replication in both islets and adrenals was not different from that in normals. Histomorphometry showed reduced volume in both the adrenal medulla and cortex in 3-month-old diabetic hamsters. In 12-month-old male and female diabetic hamsters plasma cortisol and aldosterone and 24-hour urinary epinephrine were normal, but urinary norepinephrine and dopamine levels were excessive. Thus, in contrast to what is found in the obese-hyperglycemic mouse, there was no increased islet cell DNA replication in response to the increased functional demand in the diabetic Chinese hamster. The transiently decreased DNA replication in the youngest animals may contribute to the reduced islet volume later in life. Also, in contrast to the findings in obese-hyperglycemic mice, adrenal weights were decreased and adrenal-cortex function appeared to be normal in the diabetic hamsters. Perhaps this lack of adrenal enlargement is one significant factor for the lack of adaptive islet growth in the diabetic hamster.

Cadmium‐Metallothionein Nephrotoxicity is Increased in Genetically Diabetic as Compared with Normal Chinese Hamsters

“…In this study, diabetic Chinese hamsters had normal to elevated plasma insulin levels, and this diabetic subline is known for excessive plasma glucagon levels (Gerritsen 1982;Iwashima et al 1985). In this diabetic subline cortisol, aldosterone and dehydroepiandrosterone sulfate levels in plasma are not different from normal (Frankel et al 1993), and other adrenal hormones have not been measured in the plasma of diabetic Chinese hamsters. However, 24-hour urinary levels of norepinephrine are increased in the diabetic hamster (Frankel et al 1993).…”

“…In this diabetic subline cortisol, aldosterone and dehydroepiandrosterone sulfate levels in plasma are not different from normal (Frankel et al 1993), and other adrenal hormones have not been measured in the plasma of diabetic Chinese hamsters. However, 24-hour urinary levels of norepinephrine are increased in the diabetic hamster (Frankel et al 1993). Apparently the glucagon and adrenal hormones were not suf-ficiently elevated to induce the synthesis of protective amounts of metallothionein.…”