Does insulin species modify counterregulatory hormone response to hypoglycemia?

OBJECTIVE: To examine whether pork and human insulin induce different counterregulatory responses to hypoglycemia. RESEARCH DESIGN AND METHODS: The responses to a mild hypoglycemic stimulus were determined in 35 healthy young adults with the glucose-clamp technique to ensure standardization of glucose and insulin levels. Either pork (n = 15) or human (n = 20) regular insulin was infused (0.8 mU.kg-1.min-1) to lower plasma glucose from 4.7 +/- 0.07 to 3.3 +/- 0.04 mM (both groups) over approximately 40 min. Plasma glucose was maintained at that level (with variable rate glucose infusion) for an additional 60 min. RESULTS: Steady-state insulin levels were similar in both groups (316 +/- 50 vs. 280 +/- 29 pM, pork vs. human). Before insulin administration, basal counterregulatory hormone levels were indistinguishable. Most importantly, after plasma glucose was lowered, hormonal responses were nearly identical. No significant differences in peak values of epinephrine (1769 +/- 404 vs. 1775 +/- 311 pM, pork vs. human), norepinephrine (1.64 +/- 0.23 vs. 1.87 +/- 0.20 nM, pork vs. human), glucagon (163 +/- 29 vs. 175 +/- 20 ng/L, pork vs. human), growth hormone (14 +/- 3 vs. 17 +/- 3 micrograms/L, pork vs. human), or cortisol (543 +/- 83 vs. 458 +/- 28 nM, pork vs. human) occurred. CONCLUSIONS: Our data suggest that pork and human insulin produce a comparable and robust hormonal response in healthy adults under conditions of controlled hypoglycemia.

Suppression of counterregulatory hormone response to hypoglycemia by insulin per se.

Although assessment of counterregulatory hormone responses to hypoglycemia relies upon insulin to lower the glucose level, it is not known if the exogenous insulin does used itself influences the magnitude of the hormone response. To assess this, 12 normal subjects randomly received 2 hypoglycemic clamp studies in which the only variable was the insulin dose (0.6 or 5.0 mU/kg-min). Despite 10-fold differences in circulating insulin (265 +/- 29 vs 2576 +/- 222 pmol/L respectively), the hypoglycemic stimulus did not vary. Glucose levels fell over one hour, and then were maintained for two hours at the same hypoglycemic plateau (approximately 3.1 mmol/L for each study) by a variable glucose infusion. Although basal counterregulatory hormone levels in low and high dose studies were indistinguishable, during hypoglycemia the response of epinephrine, growth hormone, and glucagon was significantly suppressed when the degree of hyperinsulinemia was increased. We conclude that raising the magnitude of hyperinsulinemia suppresses the magnitude of the counterregulatory hormone response to hypoglycemia in normal subjects. This modulating effect of insulin per se is yet another variable in the interpretation of hypoglycemic counterregulation.

Gender influences counterregulatory hormone responses to hypoglycemia.

It has been generally assumed that counterregulatory hormone responses to hypoglycemia are not influenced by gender. To test this assumption, we analyzed three separate hypoglycemic insulin clamp studies in age-matched, healthy, non-obese females (n = 33) and males (n = 37). In one study (12 females, 17 males), plasma glucose level was rapidly decreased to about 57 mg/dL for 100 minutes with a 0.65-mU/kg/min insulin infusion. Despite an identical decrease in glucose level, the increase in epinephrine (361 +/- 64 v 188 +/- 38 pg/mL, P < .05), norepinephrine (132 +/- 28 v 47 +/- 19 pg/mL, P < .01), and growth hormone ([GH] 16.0 +/- 3.8 v 4.9 +/- 1.9 ng/mL, P < .05) levels, but not glucagon or cortisol levels, were significantly greater in males than in females, respectively. In the second study (10 females, eight males), a 5.0-mU/kg/min insulin infusion was used to decrease glucose levels to 55 mg/dL for 180 minutes. Epinephrine (P < .05) and GH (P < .01) responses were greater in males than in females. In a third study (11 females, 12 males), plasma glucose level was gradually decreased to about 50 mg/dL over 240 minutes. Again epinephrine (P < .01), norepinephrine (P < .01), GH (P < .05), and cortisol (P < .01) responses were nearly twofold greater in males (P < .01). Multivariate analysis of all 70 subjects identified gender as the most significant factor contributing to the epinephrine (P < .001) and norepinephrine (P < .005) responses, and also as a significant contributor to the GH response (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)