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    Home > Active Ingredient News > Endocrine System > Diabetes : GIP and GLP-1 enhance insulin secretion in carriers of sulfonylureas inducing mutations in hepatocellular nuclear factor 1a

    Diabetes : GIP and GLP-1 enhance insulin secretion in carriers of sulfonylureas inducing mutations in hepatocellular nuclear factor 1a

    • Last Update: 2022-09-20
    • Source: Internet
    • Author: User
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    Background: Nuclear factor 1a (HNF1A) diabetes mellitus is a single-gene subtype of diabetes, also known as type 3 adolescent mature diabetes mellitus (MODY


    Other limitations are the problem of recurrent hypoglycemia in the use of SUs in some patients, and SUs can also lead to weight gain, as observed in patients with type 2 diabetes


    Objective: In this study, the infusion rates of GLP-1 and GIP were selected to mimic the postprandial plasma levels


    Methods: 10 HNF1A mutation carriers and 10 control subjects without diabetes mellitus were enrolled for double-blind, placebo-controlled, cross-over studies, including 6-day randomized sequence experiments involving 2-hour normal blood glucose-hyperglycemia clamping, co-administration: 1) SU (glimepiride 1 mg) or placebo, combined with 2) GIP (1.


    Results: In HNF1A mutation carriers, we observed: 1) hypoinsulinemia, insulinotropic effects of GIP and GLP-1, 3) superimpotent effects on insulin secretion when combined with SU1GIP and SU1GLP-1, respectively, and 4) increased


    Table 1 Overview of HNF1A mutations, treatment, and diabetic status

    Figure 1- GIP, GLP-1, plasma glucose, and glucose infusions


    Table 2 Glucose, C-peptide, C-peptide/glucose and glucagon

     

    Figure 2—C-peptide and C-peptide/glucose


    Figure 3 - Insulin and glucagon


    Figure 4-SU and incretin interaction.


    Conclusions: Our study suggests that combination therapy with SU and incretin-based insulin may be effective


    Christensen AS, Hædersdal S, Storgaard H, et al.


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