Does GIP prevent cardiac hypertrophy and fibrosis in a diabetic mouse model?
GIP infusion inhibits cardiac hypertrophy and fibrosis in a diabetic mouse model by suppressing TGF-β2 and oxidative stress, suggesting a potential therapeutic target for diabetic cardiomyopathy.
Diabetic cardiomyopathy is associated with an increased risk for heart failure and death in patients with diabetes. We investigated here whether and how GIP attenuated cardiac hypertrophy and fibrosis in diabetic mice with obesity. Diabetic db/db mice at 7 weeks old were infused with vehicle or GIP (50 nmol/kg/day) for 6 weeks, and hearts were collected for histological and RT-PCR analyzes. Cardiomyocytes isolated from neonatal mice were incubated with or without 300 nM D-Ala2-GIP, 30 mM glucose, or 100 μg/mL advanced glycation end products (AGEs) for RT-PCR and lucigenin assays. Compared with non-diabetic mice, diabetic mice exhibited larger left ventricle wall thickness and cardiomyocyte sizes and more fibrotic areas in association with up-regulation of myosin heavy chain β (β-Mhc) and transforming growth factor-beta2 (Tgf-β2) mRNA levels, all of which were inhibited by GIP infusion. High glucose increased NADPH oxidase-driven superoxide generation and up-regulated β-Mhc, Tgf-β2, and receptor for AGEs mRNA levels in cardiomyocytes, and augmented the AGE-induced β-Mhc gene expression. D-Ala2-GIP attenuated all of the deleterious effects of high glucose and/or AGEs on cardiomyocytes. Our present findings suggest that GIP could inhibit cardiac hypertrophy and fibrosis in diabetic mice via suppression of TGF-β2.
Hiromura et al. (2021) studied this question.