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OBJECTIVE Obesity is characterized by hypertrophy and pathological expansion of adipocytes with impaired insulin signaling causing insulin resistance (IR) and metabolic dysfunction. We recently reported decreased expression of glucose transporter-4 (GLUT4) in cultured adipocytes from visceral and abdominal subcutaneous fat depots from patients with morbid obesity and hyperinsulinemia (MOW) and with Type 2 diabetes (MODM). Subsequently, we wanted to study the molecular mechanisms of the glucose transport regulators, p85PI3K, Rab5 and Gapex5 in morbid obesity. PATIENTS AND METHODS Primary in vitro adipocyte cultures were developed from surgical biopsies from visceral (Visc) and abdominal (Sub) and gluteal subcutaneous (Glut) fat depots from 20 lean adults and 36 adults with morbid obesity divided into two groups: 20 with MOW and 16 MODM). mRNA and protein expression (P) of p85PI3K, Rab5 and Gapex5 were studied with RT-PCR and Western Immunoblotting (WI), respectively. RESULTS In Sub, the P of (1) p85PI3K and Gapex5 were increased in MODM and (2) Rab5 was decreased in MOW and MODM compared to the lean. In Glut, the P of p85PI3K, Rab5 and Gapex5 showed no difference between the lean and MODM. CONCLUSIONS In Sub of MODM (1) reduced RAB5 may possibly contribute to IR and glucose transport dysfunction, (2) increased Gapex5 may be a response to decreased Rab5 in an attempt to increase glucose transport and (3) increased p85PI3K may enhance IR mediating lipid accumulation in MODM. In Glut of MODM, though, the expression of p85PI3K, Rab5 and Gapex5 seems to be similar to that found in lean individuals.