1762-P: Insulin Receptor Isoforms in Human Adipose Tissue and Adipose Stem Cells
Authors: GENCHI VALENTINA ANNAMARIA , CIGNARELLI ANGELO , PERRINI SEBASTIO , PORRO STEFANIA , CACCIOPPOLI CRISTINA , NATALICCHIO ANNALISA , LAVIOLA LUIGI , GIORGINO FRANCESCO 
Published: June 2019

Insulin regulates the development and metabolism of adipose tissue (AT) by activating its tyrosine kinase receptor in this tissue. The insulin receptor (IR) consists of two isoforms, a short isoform (IR-A) with prevalent mitogenic property and a long isoform (IR-B) with prevalent metabolic activity. We investigated the expression of IR-A and IR-B in human AT and adipocyte precursors. Biopsies of abdominal subcutaneous AT (S-AT) and visceral AT (V-AT) were obtained from subjects with different BMI. Adipose-derived stem cells (ASC) were also isolated from both AT depots, and were analyzed before and after differentiation into adipocytes (dASC). mRNA levels of IR-A were 2-fold and 3-fold higher compared to IR-B in S-AT and V-AT, respectively. Total IR and IR-A mRNA levels were also 2-fold higher in S-ASC compared to V-ASC. Accordingly, S-ASC exhibited a greater insulin-induced Akt phosphorylation (4-fold) as compared to V-ASC. IR-A expression displayed a positive correlation with BMI in S-ASC (r = 0.50; p = 0.04) but not in V-ASC, in which an inverse correlation was noted (r = -0.66; p = 0.01). Adipocyte differentiation in the presence of human insulin was associated with increased mRNA expression of IR-A in both S-dASC (3-fold) and V-dASC (2.8-fold), and of total IR (5-fold) and IR-B (2-fold) only in S-dASC. Moreover, S-dASC showed higher IR-A mRNA expression (2.5-fold) when compared to V-dASC, similarly to S-ASC and S-AT. In V-dASC, but not in S-dASC, the extent of lipogenesis assessed by oil-Red-O staining was positively correlated with basal expression of total IR (r = 0.94; p = 0.04), while adipogenesis measured by Nile red fluorescent staining showed a correlation with the pAkt/pErk ratio (r = 0.95; p &lt; 0.01).

In conclusion, expression of total IR, IR-A and IR-B differs in relation to the stage of tissue development (ASC, dASC, AT) and in a depot-related manner (S vs. V). IR-A appears to be the prevalent IR isoform in human AT and adipocyte precursors and to be particularly involved in the expansion of S-AT in human obesity.

Disclosure

V. Genchi: None. A. Cignarelli: Consultant; Self; Eli Lilly and Company. Speaker's Bureau; Self; Merck Sharp & Dohme Corp., Novo Nordisk A/S. S. Perrini: None. S. Porro: None. C. Caccioppoli: None. A. Natalicchio: Other Relationship; Self; Novo Nordisk Inc., Sanofi-Aventis. L. Laviola: Advisory Panel; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc. Board Member; Self; AstraZeneca, Roche Diabetes Care, Sanofi-Aventis. Speaker's Bureau; Self; Medtronic, Mundipharma, Takeda Pharmaceutical Company Limited. F. Giorgino: Advisory Panel; Self; Aegerion Pharmaceuticals, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MedImmune, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Roche Diabetes Care, Sanofi. Consultant; Self; Roche Diabetes Care, Sanofi. Research Support; Self; Eli Lilly and Company, LifeScan, Inc., Takeda Pharmaceutical Company Limited. Other Relationship; Self; AstraZeneca, Eli Lilly and Company, Sanofi.