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207-OR: Liver-Preadipocyte Cross Talk Reverses Lipodystrophy-Induced Insulin Resistance
- Source :
- Diabetes. 69
- Publication Year :
- 2020
- Publisher :
- American Diabetes Association, 2020.
-
Abstract
- Insulin and IGF1 receptors (IR/IGF1R) control adipose tissue development. We previously demonstrated that mice with an inducible adipocyte-specific knockout of IR/IGFR (Ai-DKO) develop severe lipodystrophy, insulin resistance, glucose intolerance, hepatosteatosis, islet hyperplasia with hyperinsulinemia. This phenotype resolves over 10-30 days due to proliferation of preadipocytes (PAds) and regeneration of adipose tissue. Here, we sought to identify circulating factors that trigger PAds proliferation by treating primary wild type PAds with serum from either WT or Ai-DKO mice. To exclude the hyperglycemia effect, we also incubated cells with serum from WT and Ai-DKO mice treated with the SGLT2 inhibitor Remogliflozin (Remo). Serum from either, chow or Remo-treated Ai-DKO mice, induced primary PAds proliferation of approximately 30%. Serum proteomics analysis revealed that Cathepsin D and multiple apolipoproteins, including C2 and C3, were significantly upregulated in Ai-DKO serum (FC>1 and FDR Disclosure B. Brandao: None. M. Sakaguchi: None. T.M. Batista: None. W. Qian: None. C. Kahn: Advisory Panel; Self; ERX Pharmaceuticals, Kaleido Biosciences. Consultant; Self; AntriaBio, Flagship Pioneering, Sana-Cobalt. Funding National Institutes of Health (R01DK082659-11)
- Subjects :
- geography
medicine.medical_specialty
geography.geographical_feature_category
business.industry
Endocrinology, Diabetes and Metabolism
Insulin
medicine.medical_treatment
Adipose tissue
Hyperplasia
Islet
medicine.disease
Endocrinology
Insulin resistance
Downregulation and upregulation
Internal medicine
Internal Medicine
medicine
Hyperinsulinemia
Lipodystrophy
business
Subjects
Details
- ISSN :
- 1939327X and 00121797
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi...........e64f7ff145471b6702b8b05a5b6d8640