Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes - PubMed (original) (raw)
Pioglitazone reduces hepatic fat content and augments splanchnic glucose uptake in patients with type 2 diabetes
Mandeep Bajaj et al. Diabetes. 2003 Jun.
Abstract
The effect of pioglitazone on splanchnic glucose uptake (SGU), endogenous glucose production (EGP), and hepatic fat content was studied in 14 type 2 diabetic patients (age 50 +/- 2 years, BMI 29.4 +/- 1.1 kg/m(2), HbA(1c) 7.8 +/- 0.4%). Hepatic fat content (magnetic resonance spectroscopy) and SGU (oral glucose load- insulin clamp technique) were quantitated before and after pioglitazone (45 mg/day) therapy for 16 weeks. Subjects received a 7-h euglycemic insulin (100 mU. m(-2). min(-1)) clamp, and a 75-g oral glucose load was ingested 3 h after starting the insulin clamp. Following glucose ingestion, the steady-state glucose infusion rate during the insulin clamp was decreased appropriately to maintain euglycemia. SGU was calculated by subtracting the integrated decrease in glucose infusion rate during the 4 h after glucose ingestion from the ingested glucose load. 3-[(3)H]glucose was infused during the initial 3 h of the insulin clamp to determine rates of EGP and glucose disappearance (R(d)). Pioglitazone reduced fasting plasma glucose (10.0 +/- 0.7 to 7.5 +/- 0.6 mmol/l, P < 0.001) and HbA(1c) (7.8 +/- 0.4 to 6.7 +/- 0.3%, P < 0.001) despite increased body weight (83 +/- 3 to 86 +/- 3 kg, P < 0.001). During the 3-h insulin clamp period before glucose ingestion, pioglitazone improved R(d) (6.9 +/- 0.5 vs. 5.2 +/- 0.5 mg. kg(-1). min(- 1), P < 0.001) and insulin-mediated suppression of EGP (0.21 +/- 0.04 to 0.06 +/- 0.02 mg. kg(-1). min(-1), P < 0.01). Following pioglitazone treatment, hepatic fat content decreased from 19.6 +/- 3.6 to 10.4 +/- 2.1%, (P < 0.005), and SGU increased from 33.0 +/- 2.8 to 46.2 +/- 5.1% (P < 0.005). Pioglitazone treatment in type 2 diabetes 1) decreases hepatic fat content and improves insulin-mediated suppression of EGP and 2) augments splanchnic and peripheral tissue glucose uptake. Improved splanchnic/peripheral glucose uptake and enhanced suppression of EGP contribute to the improvement in glycemic control in patients with type 2 diabetes.
Similar articles
- Decreased plasma adiponectin concentrations are closely related to hepatic fat content and hepatic insulin resistance in pioglitazone-treated type 2 diabetic patients.
Bajaj M, Suraamornkul S, Piper P, Hardies LJ, Glass L, Cersosimo E, Pratipanawatr T, Miyazaki Y, DeFronzo RA. Bajaj M, et al. J Clin Endocrinol Metab. 2004 Jan;89(1):200-6. doi: 10.1210/jc.2003-031315. J Clin Endocrinol Metab. 2004. PMID: 14715850 - Improved glycemic control and enhanced insulin sensitivity in type 2 diabetic subjects treated with pioglitazone.
Miyazaki Y, Mahankali A, Matsuda M, Glass L, Mahankali S, Ferrannini E, Cusi K, Mandarino LJ, DeFronzo RA. Miyazaki Y, et al. Diabetes Care. 2001 Apr;24(4):710-9. doi: 10.2337/diacare.24.4.710. Diabetes Care. 2001. PMID: 11315836 Clinical Trial. - Free fatty acids reduce splanchnic and peripheral glucose uptake in patients with type 2 diabetes.
Bajaj M, Pratipanawatr T, Berria R, Pratipanawatr W, Kashyap S, Cusi K, Mandarino L, DeFronzo RA. Bajaj M, et al. Diabetes. 2002 Oct;51(10):3043-8. doi: 10.2337/diabetes.51.10.3043. Diabetes. 2002. PMID: 12351445 Clinical Trial. - [Clinical evaluation of pioglitazone].
Kobayashi M, Iwata M, Haruta T. Kobayashi M, et al. Nihon Rinsho. 2000 Feb;58(2):395-400. Nihon Rinsho. 2000. PMID: 10707564 Review. Japanese.
Cited by
- Emerging treatments for post-transplantation diabetes mellitus.
Jenssen T, Hartmann A. Jenssen T, et al. Nat Rev Nephrol. 2015 Aug;11(8):465-77. doi: 10.1038/nrneph.2015.59. Epub 2015 Apr 28. Nat Rev Nephrol. 2015. PMID: 25917553 Review. - Pioglitazone increases whole body insulin sensitivity in obese, insulin-resistant rhesus monkeys.
Tozzo E, Bhat G, Cheon K, Camacho RC. Tozzo E, et al. PLoS One. 2015 May 8;10(5):e0126642. doi: 10.1371/journal.pone.0126642. eCollection 2015. PLoS One. 2015. PMID: 25954816 Free PMC article. - The Insulin-Sensitizer Pioglitazone Remodels Adipose Tissue Phospholipids in Humans.
Palavicini JP, Chavez-Velazquez A, Fourcaudot M, Tripathy D, Pan M, Norton L, DeFronzo RA, Shannon CE. Palavicini JP, et al. Front Physiol. 2021 Dec 2;12:784391. doi: 10.3389/fphys.2021.784391. eCollection 2021. Front Physiol. 2021. PMID: 34925073 Free PMC article. - Effects of a novel selective peroxisome proliferator-activated receptor-α modulator, pemafibrate, on hepatic and peripheral glucose uptake in patients with hypertriglyceridemia and insulin resistance.
Matsuba I, Matsuba R, Ishibashi S, Yamashita S, Arai H, Yokote K, Suganami H, Araki E. Matsuba I, et al. J Diabetes Investig. 2018 Nov;9(6):1323-1332. doi: 10.1111/jdi.12845. Epub 2018 Apr 26. J Diabetes Investig. 2018. PMID: 29603684 Free PMC article. Clinical Trial. - Scaffold Implant Into the Epididymal Adipose Tissue Protects Mice From High Fat Diet Induced Ectopic Lipid Accumulation and Hyperinsulinemia.
Hendley MA, Isely C, Murphy KP, Hall HE, Annamalai P, Gower RM. Hendley MA, et al. Front Bioeng Biotechnol. 2020 Jun 16;8:562. doi: 10.3389/fbioe.2020.00562. eCollection 2020. Front Bioeng Biotechnol. 2020. PMID: 32612981 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous