Abstract 576 Poster Session II, Sunday, 5/2 (poster 204)

We have shown a marked reduction in insulin mediated glucose uptake after puberty is dependent on the development of fat depot ( Am. J. Physiol. 1997; 273:R1534). We now tested if this insulin resistance leads to an adaptive increase in the capacity of the β-cells to secrete insulin, and whether this adaptation is common to stimuli like glucose and free fatty acids (FFA) in postpubertal rats. We studied chronically catheterized, awake, Sprague Dawley rats (n=22) before puberty (PRE: determined by body weight < 90g, and the lack of testicular descent) (n=13) and after puberty (POST) (n=9) using the hyperglycemic clamp technique. PRE and POST-pubertal rats received a variable infusion of 25% dextrose to clamp the glucose plasma level at 300 mg/dl, and a primed continuous infusion of 20% intralipid (IL; plasma FFA level 1.5 mmol/l, plasma glucose levels 200 mg/dl) for 90 minutes. Results (*p= <0.05 **p=<0.002): (Table)

Table 1 No caption available.

In summary: 1) POST-pubertal rats developed marked insulin resistance reflected by decrease in MCR to 1/3 of the PRE-pubertal. 2) In POST rats the ability to secrete insulin in response to maximally stimulated glucose levels increased more than 2 fold. 3) Similarly, in POST rats the ability to secrete insulin in response to stimulated FFA levels increased more than 2.5 fold.

We conclude: 1) The development of fat and insulin resistance after puberty causes an increase in the capacity to secrete insulin in response to nutrient stimuli. 2) It is possible that a mal-adaptive response at this stage of development, may compromise a future ability of the β-cell to respond to the insulin resistance associated with obesity, and may lead to the development of Type II diabetes.