Horm Metab Res 2009; 41(10): 767-772
DOI: 10.1055/s-0029-1220751
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Factors in Serum from Type 2 Diabetes Patients Can Cause Cellular Insulin Resistance

F. Renström1 , J. Burén1 , M. K. Svensson1 , 2 , J. W. Eriksson1 , 2 , 3
  • 1Department of Public Health and Clinical Medicine, Medicine, Umeå University Hospital, Umeå, Sweden
  • 2Department of Molecular and Clinical Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden
  • 3AstraZeneca R & D, Mölndal, Sweden
Further Information

Publication History

received 17.10.2008

accepted 09.04.2009

Publication Date:
03 June 2009 (online)

Abstract

This pilot study was aimed to investigate whether there are humoral factors in serum from type 2 diabetic subjects that, in addition to glucose, insulin and free fatty acids are able to induce or contribute to peripheral insulin resistance with respect to glucose transport. Isolated subcutaneous adipocytes from 11 type 2 diabetic subjects and 10 nondiabetic controls were incubated for 24-h in medium supplemented with 25% serum from a control or a type 2 diabetic donor, in the presence of a low (5 mM) or a high (15 mM) glucose concentration, respectively. After the incubation period glucose uptake capacity was assessed. Serum from type 2 diabetic donors, compared to serum from controls, significantly reduced the maximal insulin effect to stimulate glucose uptake (∼40%, p<0.05) in adipocytes from control subjects, independent of surrounding glucose concentrations. Glucose uptake capacity in adipocytes isolated from type 2 diabetic subjects was similar regardless of culture condition. No significant alterations were found in cellular content of key proteins in the insulin signaling cascade (insulin receptor substrate-1 and -2, and glucose transporter 4) that could explain the impaired insulin-stimulated glucose transport in control adipocytes incubated with serum from type 2 diabetic donors. The present findings indicate the presence of biomolecules in the circulation of type 2 diabetic subjects, apart from glucose, insulin, and free fatty acids with the ability to induce peripheral insulin resistance. This further implies that even though normoglycemia is achieved other circulating factors can still negatively affect insulin sensitivity in type 2 diabetic patients.

References

Correspondence

Dr. F. Renström

Department of Public Health and Clinical Medicine

Umeå University Hospital

6M, 4th floor

901 85 Umeå

Sweden

Phone: +46/90/785 14 89

Fax: +46/90/785 44 00

Email: [email protected]