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January 1, 2013Cardiovascular DiabetologyOpen Access

Antidiabetic treatment restores adiponectin serum levels and APPL1 expression, but does not improve adiponectin-induced vasodilation and endothelial dysfunction in Zucker diabetic fatty rats

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Key result

Insulin or metformin fails to improve adiponectin-induced vasodilation or endothelial dysfunction in diabetic rats.

  • n=26

Why the study?

Does antidiabetic treatment with insulin or metformin improve adiponectin-induced vasodilation and endothelial dysfunction in Zucker diabetic fatty rats?

Population

20 male Zucker diabetic fatty (ZDF) rats and 6 male Zucker lean (ZL) rats, studied from 11 to 22 weeks of age.

Comparison

Antidiabetic treatment with either subcutaneous… vs Untreated ZDF rats and untreated normoglycemic…

Design

Preclinical

Follow-up

11 weeks

Authors

PSPeter SchmidMRMarkus ReschCSChristian Schach

Discussion

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Overview

Impaired adiponectin vasodilation in diabetic rats; leaves open whether antidiabetic therapy restores endothelial function in humans.

Structured PICO

Does antidiabetic treatment with insulin or metformin improve adiponectin-induced vasodilation and endothelial dysfunction in Zucker diabetic fatty rats?

P
Population
26 male Zucker lean and Zucker diabetic fatty rats followed from 11 to 22 weeks of age to assess the effects of insulin or metformin on endothelial function.
I
Intervention
Antidiabetic treatment with either subcutaneous insulin (dose adjusted to blood glucose) or oral metformin (300-600 mg/kg/day) from week 11 to 22.
C
Comparator
Untreated ZDF rats and untreated normoglycemic ZL rats.
O
Outcome
Direct vasodilatory response of isolated mesenteric resistance arteries to adiponectin and endothelium-dependent/independent function.surrogate

Main Result

Absolute Event Rate: 19% vs 18%

Antidiabetic treatment with insulin or metformin in a diabetic rat model restores adiponectin levels but fails to improve endothelial dysfunction, highlighting complex vascular signaling alterations in diabetes.

Limitations

  • Ex vivo setting for vasodilation assessment
  • ZDF rat model phenotype is based on a leptin receptor mutation, limiting human applicability
  • Potential confounding by genetic differences between ZL and ZDF rats
  • Expression analyses limited to mRNA level due to small vessel size
  • Ex vivo setting for vasodilation assessment, limiting conclusions about in vivo effects

Cite This Study

Schmid et al. (2013) studied Type 2 diabetes mellitus (n=26). Insulin or Metformin vs. Untreated Zucker diabetic fatty rats was evaluated on Maximum adiponectin-induced vasodilation. Antidiabetic treatment with insulin or metformin restored adiponectin serum levels but did not improve adiponectin-induced vasodilation or endothelial dysfunction in Zucker diabetic fatty rats.

synapsesocial.com/papers/6aa2eff4c1342f4f607f6c26https://doi.org/10.1186/1475-2840-12-46
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Metformin restores endothelial function in aorta of diabetic rats2011 · 175 citations
  2. 2Adiponectin, Change in Adiponectin, and Progression to Diabetes in the Diabetes Prevention Program2008 · 163 citations
  3. 3Impact of treatment with metformin on adipokines in patients with polycystic ovary syndrome.2010 · 29 citations
  4. 4A Novel Serum Protein Similar to C1q, Produced Exclusively in Adipocytes1995 · 3,259 citations
  5. 5Insulin Decreases Human Adiponectin Plasma Levels2002 · 118 citations