SynopsisYellow KK mice, carrying the yellow obese gene (Ay), developed marked adiposity and diabetic symptoms in comparison with their control littermates, black KK mice. The blood glucose and circulating insulin levels were increased progressively from 5 weeks of age in yellow KK mice. Age dependent alterlations were also observed in pancreas and kidney. Namely, degranulation and glycogen infiltration of B cells, first observed at 5 weeks of age, were followed by hypertrophy and central cavitation of islets. Renal glomerular changes, which were very similar to diffuse or exudative type of sclerosis in human diabetes, were also recognized in the mice at 16 weeks of age. These changes, though less remarkable, were also noted in their control littermates older than 16 weeks of age. Some metabolic defects were developed, as demonstrated by in vitro experiments. At younger age, lipogenesis by liver and adipose tissue was increased in yellow KK mice, but there was no noticeable difference in glucose oxidation by adipose tissue between both mice. Insulin sensitivity of adipose tissue was decreased with age in both mice, especially in yellow KK mice being reduced more remarkably to its complete loss at 16 weeks of age. These findings indicate that the yellow obese gene not only induces adiposity but also accelerates development of diabetic traits of KK mice. A possible mechanism for the observed diabetogenic action of the gene will be discussed.

The fa-gene was transferred from the Zucker rat (13 M strain) to the Wistar Kyoto (WKY) rat. The survey, performed at the 10th generation of backcrossing, showed that Wistar fatty rats (fa/fa), a congenic strain of WKY, developed obesity and obesity-related features, such as hyperinsulinemia and hyperlipemia, in the same manner as Zucker fatty rats. Males, but not females, showed hyperglycemia, glucosuria, and polyuria as early as 8 wk of age. Tolerance and insulin response to oral glucose were decreased with advancing age in males. The diabetic changes appeared to be caused by an interaction between predisposition to develop diabetes in the WKY rat and fa-induced obesity. This is because WKY rats were found to be less sensitive to insulin than Zucker rats by both the glucose tolerance test and the steady-state blood glucose method which estimates overall insulin sensitivity.

No abstract

The development of malignant hypertension was studied in stroke-prone spontaneously hypertensive rats (SHR) kept on 1% NaCl as drinking water. Along with salt-loading, blood pressure gradually increased and reached a severe hypertensive level (greater than 230 mmHg), which was followed by increases in urinary protein (greater than 100 (mg/250 g body wt)/day) and plasma renin concentration (PRC, from 18.9 +/- 0.1 to 51.2 +/- 19.4 (ng/ml)/h, mean +/- SD). At this stage, renal small arteries and arterioles showed severe sclerosis and fibrinoid necrosis. Stroke was observed within a week after the onset of these renal abnormalities. The dose of exogenous angiotensin II (AII) producing 30 mmHg rise in blood pressure increased with the elevation of PRC, from 22 +/- 12 to 75 +/- 36 ng/kg, which was comparable to that in rats on water. The fall of blood pressure due to an AII inhibitor, [1-sarcosine, 8-alanine]AII (10(microgram/kg)/min for 40 min) became more prominent with the increase in PRC in salt-loaded rats, but was not detected in rats on water. These findings suggest that the activation of renin-angiotensin system participates in malignant hypertension of salt-loaded stroke-prone SHR rats that show stroke signs, proteinuria, hyperreninemia, and renovascular changes.

No abstract