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 < 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.


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.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at