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Cited by 488Pancreatic function and diabetesDiabetes Treatment and ManagementDiabetes Management and Research

The Effect of Insulin Treatment on Insulin Secretion and Insulin Action in Type II Diabetes Mellitus

Garvey, W Timothy, Olefsky, J M, Griffin, J, Hamman, R F, Kolterman, O G·1985·Diabetes
DOI 10.2337/diab.34.3.222
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Abstract

We have studied the effects of 3 wk of continuous subcutaneous insulin infusion (CSII) on endogenous insulin secretion and action in a group of 14 type II diabetic subjects with a mean (±SEM) fasting glucose level of 286 ± 1 7 mg/dl. Normal basal and postprandial glucose levels were achieved during insulin therapy at the expense of marked peripheral hyperinsulinemia. During the week of posttreatment evaluation, the subjects maintained a mean fasting glucose level of 155 ± 11 mg/dl off insulin therapy, indicating a persistent improvement in carbohydrate homeostasis. Adipocyte insulin binding and in vivo insulin doseresponse curves for glucose disposal using the euglycemic clamp technique were measured before and after therapy to assess the effect on receptor and postreceptor insulin action. Adipocyte insulin binding did not change. The insulin dose-response curve for overall glucose disposal remained right-shifted compared with age-matched controls, but the mean maximal glucose disposal rate increased by 74% from 160 ± 14 to 278 ± 18 mg/m2min (P < 0.0005). The effect of insulin treatment on basal hepatic glucose output was also assessed; the mean rate was initially elevated at 159 ± 8 mg/m2/min but fell to 90 ± 5 mg/m2/min in the posttreatment period (P < 0.001), a value similar to that in control subjects. Endogenous insulin secretion was assessed in detail and found to be improved after exogenous insulin therapy. Mean 24-h integrated serum insulin and C-peptide concentrations were increased from 21,377 ± 2766 to 35,584 ± 4549 μU/ml/ min (P < 0.01) and from 1653 ± 215 to 2112 ± 188 pmol/ml/min (P < 0.05), respectively, despite lower glycemia. Second-phase insulin response to an intravenous (i.v.) glucose challenge was enhanced from 170 ± 53 to 1022 ± 376 μU/ml/min (P < 0.025), although first-phase response remained minimal. Finally, the mean insulin and C-peptide responses to an i.v. glucagon pulse were unchanged in the posttreatment period, but when glucose levels were increased by exogenous glucose infusion to approximate the levels observed before therapy and the glucagon pulse repeated, responses were markedly enhanced. Simple and multivariate correlation analysis showed that only measures of basal hepatic glucose output and the magnitude of the postbinding defect in the untreated state could be related to the respective fasting glucose levels in individual subjects. We conclude that after 3 wk of intensive insulin therapy, diabetic subjects maintain lower glucose values concomitant with: (1) partial reversal of the postbinding defect in peripheral insulin action, (2) near-normalization of basal hepatic glucose output, and (3) enhanced insulin secretory responses. First-phase insulin response remained minimal and may be a marker for the diabetic state. Correlation analysis could only implicate basal hepatic glucose output and the postbinding defect in the untreated state as direct determinants of the fasting glucose level.

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  • When plasma glucose concentrations reach the range associated with diabetes, glucose lowering is associated with improvements in both insulin sensitivity and insulin release.

    “The negative impact of glucose has been clearly shown when plasma glucose concentrations reach the range associated with diabetes. In this scenario, glucose lowering is associated with improvements in both insulin sensitivity and insulin release [140].”

    From The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes (2003) · cites this paper as [140]

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Authors
Garvey, W. T., Olefsky, J. M., Griffin, J., Hamman, R. F., & Kolterman, O. G.
Affiliations
University of California San Diego (US)
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1985-03-01
Volume
34
Issue
3
Pages
222-234
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diab.34.3.222
OpenAlex
W2100968639
Cited by
488
References
0
Citations by year
2026: 10 · 2025: 4 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 5 · 2020: 5 · 2019: 3 · 2018: 11 · 2017: 8 · 2016: 10 · 2015: 18 · 2014: 11 · 2013: 18 · 2012: 20
FWCI
38.44
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Chicago
  • National Institutes of Health (2r01am006838-23, 5r01am033649-03)
  • National Center for Research Resources (RR-00051)
  • NIH Clinical Center
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Keywords
type 2 diabetes, insulin pump therapy, insulin therapy, endogenous insulin secretion, insulin action, hyperinsulinemia, glucose disposal, hepatic glucose production, C-peptide, second-phase insulin response, carbohydrate homeostasis, insulin resistance, euglycemic clamp, glucose tolerance test
MeSH terms
Insulin Secretion, Adipose Tissue, Adult, Aged, Blood Glucose, C-Peptide, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Insulin, Insulin Infusion Systems, Insulin Resistance, Liver, Male, Middle Aged

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