Effect of insulin-like growth factor-1 on the responses to and recognition of hypoglycemia in humans: A comparison with insulin

Authors: Kerr, D., Tamborlane, W.V., Rife, F. and Sherwin, R.S.

Journal: Journal of Clinical Investigation

Volume: 91

Issue: 1

Pages: 141-147

ISSN: 0021-9738

Abstract:

Recombinant human insulin-like growth factor-1 (rhIGF-1) lowers blood glucose in humans but its effect on counterregulatory responses has not been established. We therefore compared infusions of rhIGF-1 (0.7 μg/kg per min) and insulin (0.8 mU/kg · min) for 120 min in 10 healthy volunteers (glucose allowed to fall freely). With both, glucose fell rapidly because of stimulation of glucose uptake and suppression of hepatic glucose production. Despite similar plasma glucose nadirs (2.6±0.1 vs. 2.7±0.1 mM), the glucagon response was absent (P < 0.005), growth hormone release was attenuated (P < 0.03), and norepinephrine levels were increased (P < 0.05) by rhIGF-1 compared with insulin. Absent glucagon responses were associated with a blunting of the rebound increase in glucose production (P < 0.05 vs. insulin). After stopping the infusions, glucose recovery was delayed with rhIGF-1 (P < 0.001 vs. insulin). To further evaluate the effects of rhIGF-1 during a standard hypoglycemic stimulus, eight additional healthy subjects received rhIGF-1 or insulin while glucose was clamped at 2.8 mM. Again the rise in glucagon during insulin-induced hypoglycemie was totally abolished by rhIGF-1. Growth hormone responses were delayed, whereas increases in norepinephrine, heart rate, and symptomatic awareness of hypoglycemia were greater with rhIGF-1 compared with insulin (P < 0.05). It was concluded that rhIGF-1 suppression of glucagon release during hypoglycemia impairs glucose recovery. Paradoxically, awareness of hypoglycemia is enhanced with rhIGF-1 in part due to stimulation of the sympathetic activity.

Source: Scopus

Effect of insulin-like growth factor-1 on the responses to and recognition of hypoglycemia in humans. A comparison with insulin.

Authors: Kerr, D., Tamborlane, W.V., Rife, F. and Sherwin, R.S.

Journal: J Clin Invest

Volume: 91

Issue: 1

Pages: 141-147

ISSN: 0021-9738

DOI: 10.1172/JCI116163

Abstract:

Recombinant human insulin-like growth factor-1 (rhIGF-1) lowers blood glucose in humans but its effect on counterregulatory responses has not been established. We therefore compared infusions of rhIGF-1 (0.7 micrograms/kg per min) and insulin (0.8 mU/kg.min) for 120 min in 10 healthy volunteers (glucose allowed to fall freely). With both, glucose fell rapidly because of stimulation of glucose uptake and suppression of hepatic glucose production. Despite similar plasma glucose nadirs (2.6 +/- 0.1 vs. 2.7 +/- 0.1 mM), the glucagon response was absent (P < 0.005), growth hormone release was attenuated (P < 0.03), and norepinephrine levels were increased (P < 0.05) by rhIGF-1 compared with insulin. Absent glucagon responses were associated with a blunting of the rebound increase in glucose production (P < 0.05 vs. insulin). After stopping the infusions, glucose recovery was delayed with rhIGF-1 (P < 0.001 vs. insulin). To further evaluate the effects of rhIGF-1 during a standard hypoglycemic stimulus, eight additional healthy subjects received rhIGF-1 or insulin while glucose was clamped at 2.8 mM. Again the rise in glucagon during insulin-induced hypoglycemia was totally abolished by rhIGF-1. Growth hormone responses were delayed, whereas increases in norepinephrine, heart rate, and symptomatic awareness of hypoglycemia were greater with rhIGF-1 compared with insulin (P < 0.05). It was concluded that rhIGF-1 suppression of glucagon release during hypoglycemia impairs glucose recovery. Paradoxically, awareness of hypoglycemia is enhanced with rhIGF-1 in part due to stimulation of the sympathetic activity.

Source: PubMed

Effect of insulin-like growth factor-1 on the responses to and recognition of hypoglycemia in humans. A comparison with insulin

Authors: Kerr, D., Tamborlane, W.V., Rife, F. and Sherwin, R.S.

Journal: Journal of Clinical Investigation

Volume: 91

Pages: 141-147

ISSN: 0021-9738

Abstract:

Recombinant human insulin-like growth factor-1 (rhIGF-1) lowers blood glucose in humans but its effect on counterregulatory responses has not been established. We therefore compared infusions of rhIGF-1 (0.7 micrograms/kg per min) and insulin (0.8 mU/kg.min) for 120 min in 10 healthy volunteers (glucose allowed to fall freely). With both, glucose fell rapidly because of stimulation of glucose uptake and suppression of hepatic glucose production. Despite similar plasma glucose nadirs (2.6 +/- 0.1 vs. 2.7 +/- 0.1 mM), the glucagon response was absent (P < 0.005), growth hormone release was attenuated (P < 0.03), and norepinephrine levels were increased (P < 0.05) by rhIGF-1 compared with insulin. Absent glucagon responses were associated with a blunting of the rebound increase in glucose production (P < 0.05 vs. insulin). After stopping the infusions, glucose recovery was delayed with rhIGF-1 (P < 0.001 vs. insulin). To further evaluate the effects of rhIGF-1 during a standard hypoglycemic stimulus, eight additional healthy subjects received rhIGF-1 or insulin while glucose was clamped at 2.8 mM. Again the rise in glucagon during insulin-induced hypoglycemia was totally abolished by rhIGF-1. Growth hormone responses were delayed, whereas increases in norepinephrine, heart rate, and symptomatic awareness of hypoglycemia were greater with rhIGF-1 compared with insulin (P < 0.05). It was concluded that rhIGF-1 suppression of glucagon release during hypoglycemia impairs glucose recovery. Paradoxically, awareness of hypoglycemia is enhanced with rhIGF-1 in part due to stimulation of the sympathetic activity.

Source: Manual

Preferred by: David Kerr

Effect of insulin-like growth factor-1 on the responses to and recognition of hypoglycemia in humans. A comparison with insulin.

Authors: Kerr, D., Tamborlane, W.V., Rife, F. and Sherwin, R.S.

Journal: The Journal of clinical investigation

Volume: 91

Issue: 1

Pages: 141-147

eISSN: 1558-8238

ISSN: 0021-9738

DOI: 10.1172/jci116163

Abstract:

Recombinant human insulin-like growth factor-1 (rhIGF-1) lowers blood glucose in humans but its effect on counterregulatory responses has not been established. We therefore compared infusions of rhIGF-1 (0.7 micrograms/kg per min) and insulin (0.8 mU/kg.min) for 120 min in 10 healthy volunteers (glucose allowed to fall freely). With both, glucose fell rapidly because of stimulation of glucose uptake and suppression of hepatic glucose production. Despite similar plasma glucose nadirs (2.6 +/- 0.1 vs. 2.7 +/- 0.1 mM), the glucagon response was absent (P < 0.005), growth hormone release was attenuated (P < 0.03), and norepinephrine levels were increased (P < 0.05) by rhIGF-1 compared with insulin. Absent glucagon responses were associated with a blunting of the rebound increase in glucose production (P < 0.05 vs. insulin). After stopping the infusions, glucose recovery was delayed with rhIGF-1 (P < 0.001 vs. insulin). To further evaluate the effects of rhIGF-1 during a standard hypoglycemic stimulus, eight additional healthy subjects received rhIGF-1 or insulin while glucose was clamped at 2.8 mM. Again the rise in glucagon during insulin-induced hypoglycemia was totally abolished by rhIGF-1. Growth hormone responses were delayed, whereas increases in norepinephrine, heart rate, and symptomatic awareness of hypoglycemia were greater with rhIGF-1 compared with insulin (P < 0.05). It was concluded that rhIGF-1 suppression of glucagon release during hypoglycemia impairs glucose recovery. Paradoxically, awareness of hypoglycemia is enhanced with rhIGF-1 in part due to stimulation of the sympathetic activity.

Source: Europe PubMed Central