A–E: Mechanisms underlying the blunted adiponectin secretion in adipocytes from obese/type 2 diabetic mice. A–E: Mechanisms underlying the blunted adiponectin secretion in adipocytes from obese/type 2 diabetic mice. A and B: Quantitative RT-PCR gene expression analysis in adipocytes isolated from chow-fed or HFD-fed mice. Epac2 was not detected. C: Total adiponectin content (present in the cell lysate) in subcutaneous adipocytes. The amount of released adiponectin expressed as a percentage of total adiponectin content under basal (D) and stimulated (E) conditions. The percentage of released adiponectin in E is significantly higher compared with basal levels (D) upon stimulation with FSK/IBMX (P = 0.002), epinephrine (EPI) (P = 0.004), and CL (P = 0.0002) in chow adipocytes and in HFD adipocytes after treatment with FSK/IBMX (P = 0.02). Data in A and B are from five (chow-fed) and four (HFD-fed) animals. Results in C represent 20–22 experiments, and data in D and E are from eight chow-fed and eight HFD-fed animals. *P < 0.05; **P < 0.01; ***P < 0.001. Ali M. Komai et al. Diabetes 2016;65:3301-3313 ©2016 by American Diabetes Association