Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Editorial
. 2024 Jun 1;73(6):837-843.
doi: 10.2337/dbi23-0035.

Insulin Hypersecretion as Promoter of Body Fat Gain and Hyperglycemia

Affiliations
Editorial

Insulin Hypersecretion as Promoter of Body Fat Gain and Hyperglycemia

Bettina Mittendorfer et al. Diabetes. .
No abstract available

PubMed Disclaimer

Conflict of interest statement

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Figures

None
Graphical abstract
Figure 1
Figure 1
Two competing hypotheses about the primary culprit in obesity-related insulin resistance and the common co-occurrence of insulin hypersecretion, insulin resistance, and excess adiposity.
Figure 2
Figure 2
Key metabolic differences and similarities between insulin hypersecreters and insulin normosecreters at baseline (A) and metabolic trajectories of hypersecreters compared with normosecreters (B) in the current work by Tricò et al. (14) and the previous work by Tricò et al. (15). FA, fatty acid; HECP, hyperinsulinemic-euglycemic clamp procedure; NEFA, nonesterified fatty acids; TG, triglyceride; WBISI, whole-body insulin sensitivity index.
Figure 3
Figure 3
Pathway from circulating insulin to insulin action. A: Cellular mechanisms involved in insulin action, including insulin binding to cell surface receptors, leading to insulin receptor autophosphorylation, receptor internalization, and downstream insulin signaling that ultimately causes a physiological cellular response, such as glucose uptake or glucose production. B: Alterations in insulin-insulin receptor interaction because of differences in insulin receptor number/density or insulin receptor binding affinity result in an increase or decrease in insulin sensitivity that is characterized by a leftward or rightward shift of the insulin dose-response curve. C: Alterations in intracellular insulin signal transduction result in an increase or decrease in insulin responsiveness that is characterized by a change in the slope of the insulin dose-response curve. D: Putative interindividual differences in insulin dose-response characteristics of impaired insulin action that cannot be adequately described with a single measurement of insulin action.
Figure 4
Figure 4
Cellular mechanisms involved in insulin-mediated insulin resistance include insulin receptor downregulation through internalization, excess degradation, reduced synthesis, decreased insulin-insulin receptor binding dynamics, and blunting intracellular signal transduction. IR, insulin receptor.
Figure 5
Figure 5
Regulation of plasma glucose concentration. A: Plasma glucose concentration represents the balance between the appearance rates of ingested and endogenously produced glucose in the circulation and tissue glucose uptake. B: Plasma glucose concentration is regulated by a complex interplay among plasma glucose itself, hormones (most prominently insulin and glucagon), and neural circuits, all of which can affect the appearance rates of ingested and endogenously produced glucose in the circulation and tissue glucose uptake.

Comment on

References

    1. Magkos F, Reeds DN, Mittendorfer B.. Evolution of the diagnostic value of “the sugar of the blood”: hitting the sweet spot to identify alterations in glucose dynamics. Physiol Rev 2023;103:7–30 - PMC - PubMed
    1. Bergman RN. Origins and history of the minimal model of glucose regulation. Front Endocrinol (Lausanne) 2021;11:583016. - PMC - PubMed
    1. Ferrannini E. A journey in diabetes: from clinical physiology to novel therapeutics: the 2020 Banting Medal for Scientific Achievement Lecture. Diabetes 2021;70:338–346 - PMC - PubMed
    1. Norton L, Shannon C, Gastaldelli A, DeFronzo RA.. Insulin: the master regulator of glucose metabolism. Metabolism 2022;129:155142. - PubMed
    1. Esser N, Utzschneider KM, Kahn SE.. Early beta cell dysfunction vs insulin hypersecretion as the primary event in the pathogenesis of dysglycaemia. Diabetologia 2020;63:2007–2021 - PubMed