Insulin stimulates in vivo cell proliferation in white adipose tissue

The effects of insulin on white adipose tissue hyperplasia have been studied by quantitative radioautography in streptozotocin diabetic rats. After 1 mo of diabetes, the majority of the adipocytes were extremely small (less than 15 microM) but contained several tiny triglyceride droplets (pauciadipose cells). At this point, the diabetic animals were infused with insulin (8.5 U.kg-1.day-1) delivered via osmotic minipumps for 0-8 days. Control and diabetic rats were pulse-injected with tritiated thymidine (4 h), and samples of parametrial white adipose tissue (PWAT) were collected for quantitative analysis of mitotic frequencies. One-day insulin treatment increased PWAT weight and adipocyte size without stimulating mitoses. However, after 4 days of insulin replacement, the total tissue labeling index increased greater than 120 times over control values. This marked enhancement of mitotic activity principally occurred in interstitial cells rather than in typical adipocytes, pauciadipose cells, or endothelial cells. After 8 days of insulin infusion, the mitotic activity significantly decreased. The results demonstrate that 1) insulin is able to stimulate cell proliferation in PWAT of adult diabetic rats, 2) it transiently stimulates proliferative activity in adipose tissue after a 2- to 3-day period of induction, 3) the increase in adipocyte size precedes the enhancement of mitotic activity, and 4) the effects of insulin were specific, as in the same rats, under the same experimental conditions, insulin did not increase the cell labeling in brown adipose tissue.