CoChat
Sign Up
Cited by 108Pancreatic function and diabetesDiabetes Management and ResearchDiabetes Treatment and Management

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.

Open access
Bolli, G B, Tsalikian, E, Haymond, M W, Cryer, P E, Gerich, J E·1984·Journal of Clinical Investigation
DOI 10.1172/jci111359PMC PMC437063
Open this paper in CoChat — free accountOpen PDF

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

Integrity signals

Registry

Crossref · 10.1172/jci111359

Cites

62 of 62 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In type 2 diabetes, the glucagon response to hypoglycemia has been diversely reported as being either modestly diminished or preserved.

    “In type 2 diabetes, the glucagon response to hypoglycemia has been diversely reported as being either modestly diminished (16, 30,50) or preserved (33,34,37,38).”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [30]

  • Interpretation of early studies is limited by heterogeneity of study design, differences in blood glucose nadir between the diabetic and control groups, a lack of age-matched control subjects, and the disparate methods used to induce hypoglycemia.

    “Interpretation of the early studies is limited by heterogeneity of study design (29), differences in blood glucose nadir between the diabetic and control groups (30,31), a lack of agematched control subjects (31), and the disparate methods used to induce hypoglycemia (30 -35).”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [30]

  • Plasma free fatty acids increase in response to hypoglycemia in type 2 diabetes but do not in type 1 diabetes.

    “Plasma free fatty acids increase in response to hypoglycemia in type 2 diabetes (30,33,50) but do not in type 1 diabetes (54).”

    From Hypoglycemia in Type 2 Diabetes (2005) · cites this paper as [30]

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Bolli, G. B., Tsalikian, E., Haymond, M. W., Cryer, P. E., & Gerich, J. E.
Affiliations
Mayo Clinic (US)
ORCID
Venue
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Published
1984-06-01
Volume
73
Issue
6
Pages
1532-1541
ISSN
0021-9738 (ISSN-L)
DOI
10.1172/jci111359
PMC
PMC437063
OpenAlex
W2010800358
Semantic Scholar
786d58ad6f63ba856c5f63459c3b3032b1cf5333
Cited by
108
References
57
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 6 · 2014: 7 · 2013: 2 · 2012: 3
FWCI
8.00
Type
journal article
Language
en
Open access
Locations
  • Journal of Clinical Investigation (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
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
type 2 diabetes, glucose counterregulation, hypoglycemia, glucagon secretion, insulin resistance, glucose production, glucose utilization, neuroendocrine response, epinephrine, norepinephrine, growth hormone, cortisol, endogenous insulin secretion, subcutaneous insulin
MeSH terms
Adult, Blood Glucose, Blood Pressure, C-Peptide, Diabetes Mellitus, Type 2, Female, Glucose, Glycolysis, Heart Rate, Glycated Hemoglobin, Hormones, Humans, Injections, Subcutaneous, Insulin, Kinetics, Male, Middle Aged, Reference Values

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review