S Skovsø1, J Damgaard2, J J Fels2, G S Olsen2, X A Wolf2, B Rolin2, J J Holst1. 1. Department of Biomedical Sciences, Endocrinology Research Section, Panum Institute, Copenhagen, Denmark. 2. Diabetes Research Unit, Novo Nordisk A/S, Måløv, Denmark.
Abstract
BACKGROUND/ OBJECTIVES: Insulin therapy is required for many patients with the obesity-related disorder type 2 diabetes, but is also associated with weight gain. The specific location of adipose tissue location matters to cardiovascular disease (CVD) risk. We investigated effects of exogenous insulin on fat distribution in the high-fat/high-sucrose fed rat treated with streptozotocin (HF/HS-STZ) rat model of type 2 diabetes. We also examined effects of insulin therapy on circulating CVD markers, including adiponectin, triglycerides (TGs), total cholesterol and high-density lipoprotein. SUBJECTS/ METHODS: Male SD rats were HF/HS fed for 5 weeks followed by STZ treatment to mimic the hallmarks of human obesity-associated insulin resistance followed by hyperglycemia. Magnetic resonance imaging and computed tomography were used to determine total fat, abdominal fat distribution and liver fat before and after insulin therapy in HF/HS-STZ rats. HbA1c%, TGs, cholesterol, high-density lipoprotein and adiponectin were analyzed by conventional methods adapted for rats. RESULTS: Insulin therapy lowered HbA1c (P<0.001), increased body weight (P<0.001), increased lean mass (P<0.001) and led to a near doubling of total fat mass (P<0.001), with the highest increase in subcutaneous adipose tissue as compared with visceral adipose tissue (P<0.001). No changes in liver fat were observed after insulin therapy, whereas plasma TG and cholesterol levels were decreased (P<0.001, P<0.01), while high-density lipoprotein (HDL) and adiponectin levels were elevated (P<0.01, P<0.001). CONCLUSIONS: Using the HF/HS-STZ rat as an animal model for type 2 diabetes, we find that insulin therapy modulates fat distribution. Specifically, our data show that insulin has a relatively positive effect on CVD-associated parameters, including abdominal fat distribution, lean body mass, adiponectin, TGs and HDL in HF/HS-STZ rats, despite a modest gain in weight.
BACKGROUND/ OBJECTIVES:Insulin therapy is required for many patients with the obesity-related disorder type 2 diabetes, but is also associated with weight gain. The specific location of adipose tissue location matters to cardiovascular disease (CVD) risk. We investigated effects of exogenous insulin on fat distribution in the high-fat/high-sucrose fed rat treated with streptozotocin (HF/HS-STZ) rat model of type 2 diabetes. We also examined effects of insulin therapy on circulating CVD markers, including adiponectin, triglycerides (TGs), total cholesterol and high-density lipoprotein. SUBJECTS/ METHODS: Male SD rats were HF/HS fed for 5 weeks followed by STZ treatment to mimic the hallmarks of humanobesity-associated insulin resistance followed by hyperglycemia. Magnetic resonance imaging and computed tomography were used to determine total fat, abdominal fat distribution and liver fat before and after insulin therapy in HF/HS-STZrats. HbA1c%, TGs, cholesterol, high-density lipoprotein and adiponectin were analyzed by conventional methods adapted for rats. RESULTS:Insulin therapy lowered HbA1c (P<0.001), increased body weight (P<0.001), increased lean mass (P<0.001) and led to a near doubling of total fat mass (P<0.001), with the highest increase in subcutaneous adipose tissue as compared with visceral adipose tissue (P<0.001). No changes in liver fat were observed after insulin therapy, whereas plasma TG and cholesterol levels were decreased (P<0.001, P<0.01), while high-density lipoprotein (HDL) and adiponectin levels were elevated (P<0.01, P<0.001). CONCLUSIONS: Using the HF/HS-STZrat as an animal model for type 2 diabetes, we find that insulin therapy modulates fat distribution. Specifically, our data show that insulin has a relatively positive effect on CVD-associated parameters, including abdominal fat distribution, lean body mass, adiponectin, TGs and HDL in HF/HS-STZrats, despite a modest gain in weight.
Authors: Salim Yusuf; Steven Hawken; Stephanie Ounpuu; Leonelo Bautista; Maria Grazia Franzosi; Patrick Commerford; Chim C Lang; Zvonko Rumboldt; Churchill L Onen; Liu Lisheng; Supachai Tanomsup; Paul Wangai; Fahad Razak; Arya M Sharma; Sonia S Anand Journal: Lancet Date: 2005-11-05 Impact factor: 79.321
Authors: Julio Rosenstock; Daniel L Lorber; Luigi Gnudi; Campbell P Howard; David W Bilheimer; P-C Chang; Richard E Petrucci; Anders H Boss; Peter C Richardson Journal: Lancet Date: 2010-06-26 Impact factor: 79.321
Authors: F Galland; L Duvillard; J M Petit; L Lagrost; G Vaillant; J M Brun; P Gambert; B Vergès Journal: Diabetes Metab Date: 2006-12 Impact factor: 6.041
Authors: Arya E Mehran; Nicole M Templeman; G Stefano Brigidi; Gareth E Lim; Kwan-Yi Chu; Xiaoke Hu; Jose Diego Botezelli; Ali Asadi; Bradford G Hoffman; Timothy J Kieffer; Shernaz X Bamji; Susanne M Clee; James D Johnson Journal: Cell Metab Date: 2012-12-05 Impact factor: 27.287
Authors: David André Barrière; Christophe Noll; Geneviève Roussy; Farah Lizotte; Anissa Kessai; Karyn Kirby; Karine Belleville; Nicolas Beaudet; Jean-Michel Longpré; André C Carpentier; Pedro Geraldes; Philippe Sarret Journal: Sci Rep Date: 2018-01-11 Impact factor: 4.379
Authors: Laura J Andreasen; Rikke K Kirk; Christian Fledelius; Mark A Yorek; Jens Lykkesfeldt; Thorbjorn Akerstrom Journal: J Diabetes Res Date: 2020-08-02 Impact factor: 4.011