Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

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Hammarstedt, Ann,1975Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine (författare)

Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects

Artikel/kapitelEngelska2005

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2004-12-29
Springer Science and Business Media LLC,2005

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LIBRIS-ID:oai:gup.ub.gu.se/50405
https://gup.ub.gu.se/publication/50405URI
https://doi.org/10.1007/s00125-004-1612-3DOI

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Språk:engelska

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AIMS/HYPOTHESIS: We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPARgamma co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance. METHODS: Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic-hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot. RESULTS: Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPARgamma co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor-alpha increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects. CONCLUSIONS/INTERPRETATION: Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.

Ämnesord och genrebeteckningar

Adipocytes/drug effects/metabolism
Adiponectin
Adipose Tissue/drug effects/*physiology
Adult
Body Mass Index
Body Size
Gene Expression Regulation/drug effects
Glucose Transporter Type 4
Humans
Hypoglycemic Agents/pharmacology
Insulin Resistance/*physiology
Intercellular Signaling Peptides and Proteins/blood/genetics
Monosaccharide Transport Proteins/deficiency/genetics
Muscle Proteins/deficiency/genetics
Phosphoproteins/deficiency/genetics
Thiazolidinediones/*pharmacology

Biuppslag (personer, institutioner, konferenser, titlar ...)

Rotter Sopasakis, Victoria,1972Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine(Swepub:gu)xrotvi (författare)
Gogg, Silvia,1962Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine(Swepub:gu)xgogsi (författare)
Jansson, Per-Anders,1961Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine(Swepub:gu)xjansp (författare)
Smith, Ulf,1943Gothenburg University,Göteborgs universitet,Institutionen för invärtesmedicin, Avdelningen för internmedicin,Institute of Internal Medicine, Dept of Medicine(Swepub:gu)xsmiul (författare)
Göteborgs universitetInstitutionen för invärtesmedicin, Avdelningen för internmedicin (creator_code:org_t)

Sammanhörande titlar

Ingår i:Diabetologia: Springer Science and Business Media LLC48:1, s. 96-1040012-186X1432-0428

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Av författaren/redakt...: Hammarstedt, Ann ...; Rotter Sopasakis ...; Gogg, Silvia, 19 ...; Jansson, Per-And ...; Smith, Ulf, 1943

Artiklar i publikationen: Diabetologia

Av lärosätet: Göteborgs universitet

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