Dataset Information

Effects of gastric bypass surgery on expression of glucose transporters and fibrotic biomarkers in kidney of diabetic fatty rats.

ABSTRACT:

Background

Diabetic nephropathy is the leading cause of chronic kidney disease. Observational studies suggest Roux-en-Y gastric bypass (RYGB) reduces progression of diabetic nephropathy.

Objectives

To unravel the mechanisms by which RYGB is beneficial and protective for diabetic nephropathy.

Setting

Academic laboratories.

Methods

Forty-eight Zucker diabetic fatty rats were randomized to RYGB, sham surgery (SHAM), or pair-fed (PF) groups. An oral glucose tolerance test was performed at 25 days post intervention and kidneys were harvested at 30 days. Primary outcome measures included expression of key genes and proteins in the glucose transport, oxidative stress, inflammation, and fibrosis pathways.

Results

Thirty days post intervention, RYGB rats weighed 349 ± 8 g, which was lower than SHAM (436 ± 14 g, P < .001), but not PF (374 ± 18 g) rats. RYGB rats had lower fasting glucose than PF animals and improved homeostatic model assessment of insulin resistance compared with PF and SHAM groups. These enhanced metabolic outcomes were accompanied by reduced sodium-glucose co-transporter 1 (Sglt1) gene expression (-23% versus PF, P = .01) in the kidney of RYGB rats. Expression of Sglt2, Glut1, or Glut2 mRNA, or oxidative stress and inflammation markers did not differ significantly. However, RYGB surgery induced a 19% lower expression of transforming growth factor (Tgfβ) mRNA (P = .004) compared with SHAM treated animals. Notably, adenosine monophosphate-activated protein kinase phosphorylation was increased (P = .04) in kidneys of the RYGB surgery animals.

Conclusions

Improvement of hyperglycemia after RYGB may reduce the glucose load on the kidney leading to a downregulation of specific glucose transporters. RYGB surgery may also attenuate kidney fibrosis through the adenosine monophosphate-activated protein kinase/TGFβ pathway.

SUBMITTER: Vangoitsenhoven R

PROVIDER: S-EPMC8276306 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aims/hypothesisRoux-en-Y gastric bypass (RYGB) surgery is characterised by glycaemic variability. Prospective studies of glucose metabolism in pregnancy after RYGB are not available, therefore this study aimed to evaluate physiological alterations in glucose metabolism in pregnancy following RYGB.MethodsSixty-three pregnant women (25 who underwent RYGB, 19 non-operated obese control women and 19 normal weight control women) were included. Frequently sampled 3 h OGTTs and 1 h IVGTTs were performed between 24 and 28 weeks of gestation and, in a subgroup, were repeated at 3-6 months after delivery.ResultsWe observed major alterations in glucose kinetics during the OGTT, including an early increase in plasma glucose followed by hypoglycaemia in 90% of women who had previously undergone RYGB. The higher degree of glycaemic variability in this group was accompanied by increased insulin, C-peptide and glucagon concentrations after oral glucose load, whereas no differences in insulin response were observed after parenteral glucose administration (RYGB vs normal weight). IVGTT data suggested improved insulin sensitivity (mean difference 0.226 × 10-4 min-1 [pmol/l]-1 [95% CI 0.104, 0.348]; p < 0.001) and disposition index in pregnancies after RYGB when compared with obese control women. However, subtle alterations in insulin action and beta cell function were still observed when comparing women who had undergone RYGB with the normal-weight control group. Moreover, we observed that fetal growth was associated with maternal glucose nadir levels and insulin secretion in offspring of those who had previously undergone RYGB.Conclusions/interpretationPregnancies after RYGB are affected by altered postprandial glucose, insulin and C-peptide dynamics. Insulin sensitivity is improved by RYGB, although subtle alterations in beta cell function are observed. Longitudinal studies are needed to assess potential consequences for fetal development and pregnancy outcomes.