Mechanisms of glucagon secretion during insulin-induced hypoglycemia in man. Role of the beta cell and arterial hyperinsulinemia.

Bolli, G; De Feo, P; Perriello, G; De Cosmo, S; Compagnucci, P; Santeusanio, F; Brunetti, P; Unger, R H

doi:10.1172/jci111315

Cited by 64Pancreatic function and diabetesDiabetes Management and ResearchDiabetes Treatment and Management

Mechanisms of glucagon secretion during insulin-induced hypoglycemia in man. Role of the beta cell and arterial hyperinsulinemia.

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Bolli, G, De Feo, P, Perriello, G, De Cosmo, S, Compagnucci, P, Santeusanio, F, Brunetti, P, Unger, R H·1984·Journal of Clinical Investigation

DOI 10.1172/jci111315PMC PMC425102

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Abstract

To elucidate the mechanisms controlling the response of glucagon to hypoglycemia, a vital component of the counterregulatory hormonal response, the role of intraislet insulin was studied in seven normal subjects and five subjects with insulin-dependent diabetes mellitus (IDDM) (of less than 15-mo duration). In the normal subjects, hypoglycemia (arterial plasma glucose [PG] 53 +/- 3 mg/dl) induced by an intravenous insulin infusion (30 mU/m2 X min for 1 h, free immunoreactive insulin [FIRI] 58 +/- 2 microU/ml) elicited a 100% fall in insulin secretion and an integrated rise in glucagon of 7.5 ng/ml per 120 min. When endogenous insulin secretion was suppressed by congruent to 50 or congruent to 85% by a hyperinsulinemic-euglycemic clamp (FIRI 63 +/- 1.5 or 147 +/- 0.3 microU/ml, respectively) before hypoglycemia, the alpha cell responses to hypoglycemia were identical to those of the control study. When the endogenous insulin secretion was stimulated by congruent to 100% (hyperinsulinemic-hyperglycemic clamp, FIRI 145 +/- 1.5 microU/ml, PG 132 +/- 2 mg/dl) before hypoglycemia, the alpha cell responses to the hypoglycemia were also superimposable on those of the control study. Finally, in C-peptide negative diabetic subjects made euglycemic by a continuous overnight intravenous insulin infusion, the alpha cell responses to hypoglycemia were comparable to those of normal subjects despite absent beta cell secretion, and were not affected by antecedent hyperinsulinemia (hyperinsulinemic-euglycemic clamp for 2 h, FIRI 61 +/- 2 microU/ml). These results indicate that the glucagon response to insulin-induced hypoglycemia is independent of the level of both endogenous intraislet and exogenous arterial insulin concentration in normal man, and that this response may be normal in the absence of endogenous insulin secretion, in contrast to earlier reports. Thus, loss of beta cell function is not responsible for alpha cell failure during insulin-induced hypoglycemia in IDDM.

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Although this contrasts with a previous report of ours, it is in accordance with several recent reports.
“Although this contrasts with a previous report of ours [35], it is in accordance with several recent reports [7][8][9].”
From Relative roles of insulin and hypoglycaemia on induction of neuroendocrine responses to, symptoms of, and deterioration of cognitive function in hypoglycaemia in male and female humans (1994) · cites this paper as [35]

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Authors: Bolli, G., De Feo, P., Perriello, G., De Cosmo, S., Compagnucci, P., Santeusanio, F., Brunetti, P., & Unger, R. H.
Affiliations: University of Perugia (IT)
Mayo Clinic (US)
ORCID: Bolli, G
Perriello, G
Venue: Journal of Clinical Investigation
Publisher: American Society for Clinical Investigation
Published: 1984-04-01
Volume: 73
Issue: 4
Pages: 917-922
ISSN: 0021-9738 (ISSN-L)
DOI: 10.1172/jci111315
PMC: PMC425102
OpenAlex: W1997046391
Cited by: 64
References: 30
Citations by year: 2025: 1 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 2 · 2017: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
FWCI: 5.13
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Clinical Investigation (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Consiglio Nazionale delle Ricerche
National Institutes of Health
Fogarty International Center
Topics: Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords: glucagon secretion, insulin-induced hypoglycemia, counterregulatory response, alpha-cell function, beta-cell function, hyperinsulinemia, type 1 diabetes, hyperinsulinemic-euglycemic clamp, glucose homeostasis
MeSH terms: Adult, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 1, Glucagon, Humans, Hyperinsulinism, Hypoglycemia, Insulin, Islets of Langerhans

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Mechanisms of glucagon secretion during insulin-induced hypoglycemia in man. Role of the beta cell and arterial hyperinsulinemia.

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