Journal article
Defective glucose counterregulation after subcutaneous insulin in noninsulin-dependent diabetes mellitus. Paradoxical suppression of glucose utilization and lack of compensatory increase in glucose production, roles of insulin resistance, abnormal neuroendocrine responses, and islet paracrine interactions
The Journal of clinical investigation, Vol.73(6), pp.1532-1541
06/1984
DOI: 10.1172/JCI111359
PMCID: PMC437063
PMID: 6373827
Abstract
To characterize glucose counterregulatory mechanisms in patients with noninsulin-dependent diabetes mellitus (NIDDM) and to test the hypothesis that the increase in glucagon secretion during hypoglycemia occurs primarily via a paracrine islet A-B cell interaction, we examined the effects of a subcutaneously injected therapeutic dose of insulin (0.15 U/kg) on plasma glucose kinetics, rates of glucose production and utilization, and their relationships to changes in the circulating concentrations of neuroendocrine glucoregulatory factors (glucagon, epinephrine, norepinephrine, growth hormone, and cortisol), as well as to changes in endogenous insulin secretion in 13 nonobese NIDDM patients with no clinical evidence of autonomic neuropathy. Compared with 11 age-weight matched nondiabetic volunteers in whom euglycemia was restored primarily by a compensatory increase in glucose production, in the diabetics there was no compensatory increase in glucose production (basal 2.08 +/- 0.04---1.79 +/- 0.07 mg/kg per min at 21/2 h in diabetics vs. basal 2.06 +/- 0.04---2.32 +/- 0.11 mg/kg per min at 21/2 h in nondiabetics, P less than 0.01) despite the fact that plasma insulin concentrations were similar in both groups (peak values 22 +/- 2 vs. 23 +/- 2 microU/ml in diabetics and nondiabetics, respectively). This abnormality in glucose production was nearly completely compensated for by a paradoxical decrease in glucose utilization after injection of insulin (basal 2.11 +/- 0.03---1.86 +/- 0.06 mg/kg per min at 21/2 h in diabetics vs. basal 2.08 +/- 0.04---2.39 +/- 0.11 mg/kg per min at 21/2 h nondiabetics, P less than 0.01), which could not be accounted for by differences in plasma glucose concentrations; the net result was a modest prolongation of hypoglycemia. Plasma glucagon (area under the curve [AUC] above base line, 12 +/- 3 vs. 23 +/- 3 mg/ml X 12 h in nondiabetics, P less than 0.05), cortisol (AUC 2.2 +/- 0.5 vs. 4.0 +/- 0.7 mg/dl X 12 h in nondiabetics, P less than 0.05), and growth hormone (AUC 1.6 +/- 0.4 vs. 2.9 +/- 0.4 micrograms/ml X 12 h in nondiabetics, P less than 0.05) responses in the diabetics were decreased 50% while their plasma norepinephrine responses (AUC 49 +/- 12 vs. 21 +/- 5 ng/ml X 12 h in nondiabetics, P less than 0.05) were increased twofold (P less than 0.05) and their plasma epinephrine responses were similar to those of the nondiabetics (AUC 106 +/- 17 vs. 112 +/- 10 ng/ml X 12 h in nondiabetics). In both groups of subjects, increases in plasma glucagon were inversely correlated with plasma glucose concentrations (r = -0.80 in both groups, P less than 0.01) and suppression of endogenous insulin secretion (r = -0.57 in nondiabe
Details
- Title: Subtitle
- Defective glucose counterregulation after subcutaneous insulin in noninsulin-dependent diabetes mellitus. Paradoxical suppression of glucose utilization and lack of compensatory increase in glucose production, roles of insulin resistance, abnormal neuroendocrine responses, and islet paracrine interactions
- Creators
- Geremia B BolliEva TsalikianMorey W HaymondPhilip E CryerJohn E Gerich
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.73(6), pp.1532-1541
- DOI
- 10.1172/JCI111359
- PMID
- 6373827
- PMCID
- PMC437063
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- AM05827 / NIADDK NIH HHS AM20411 / NIADDK NIH HHS RR00585 / NCRR NIH HHS
- Language
- English
- Date published
- 06/1984
- Academic Unit
- Stead Family Department of Pediatrics; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984093219702771
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