Increased responses of glucagon and glucose production to hypoglycemia with intraperitoneal versus subcutaneous insulin treatment

The study aim was to investigate the effect of the route of insulin treatme nt on the glucagon and glucose production (GP) responses to hypoglycemia in the diabetic rat. Experiments were performed in 4 groups of rats: (1) stre ptozotocin (STZ)-induced diabetic, untreated (D, n = 7), (2) diabetic treat ed with subcutaneous insulin (DSC, n = 8), (3) diabetic treated with intrap eritoneal insulin (DIP, n = 6), and (4) normal control (N, n = 10). Slow-re lease insulin implants were used in DSC and DIP rats for 10 to 14 days (3 U /d). A hyperinsulinemic (120 pmol . kg(-1) . min(-1) insulin)-hypoglycemic (glycemia = 2.5 +/- 0.1 mmol/L) clamp following an isoglycemic basal period was performed in 5-hour fasted rats. Basal plasma glucose was normalized i n both DSC and DIP rats; however, in DSC but not DIP rats, glucose normaliz ation required peripheral hyperinsulinemia. Tracer-determined GP, which was elevated in D rats, was completely normalized in DIP but only partially co rrected in DSC rats. Basal glucagon levels were similar in all groups. Duri ng hypoglycemia, GP was suppressed in D rats (Delta, -28.9 +/- 5.0 mu mol . kg(-1) . min(-1)), moderately increased in DSC rats (Delta, 6.1 +/- 5.6, P < .01 v D), but markedly increased in DIP and N rats (Delta, 34.5 +/- 4.5 for DIP and 16.8 +/- 2.8 for N; P < .01 v D, P < .05 for DIP v DSC or N). P lasma glucagon increased 6-fold in N (945 +/- 129 pg/mL), only doubled in D (424 +/- 54), and tripled in DSC (588 +/- 83), but increased 5-fold in DIP rats (1,031 +/- 75, P < .05 v D and DSC). We conclude that in STZ-diabetic rats, (1) intraperitoneal but not subcutaneous insulin treatment normalize s basal GP and (2) intraperitoneal insulin treatment as compared with subcu taneous treatment alleviates peripheral hyperinsulinemia and results in inc reased glucagon and GP responses to hypoglycemia. Copyright (C) 2000 by W.B . Saunders Company.