Uteroplacental insufficiency down regulates insulin receptor and affects expression of key enzymes of long-chain fatty acid (LCFA) metabolism in skeletal muscle at birth

Germani, Daniela; Puglianiello, Antonella; Cianfarani, Stefano
January 2008
Cardiovascular Diabetology;2008, Vol. 7, p1
Academic Journal
Background: Epidemiological studies have revealed a relationship between early growth restriction and the subsequent development of insulin resistance and type 2 diabetes. Ligation of the uterine arteries in rats mimics uteroplacental insufficiency and serves as a model of intrauterine growth restriction (IUGR) and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia and adiposity in the offspring. The objective of this study was to investigate the effects of uterine artery ligation on the skeletal muscle expression of insulin receptor and key enzymes of LCFA metabolism. Methods: Bilateral uterine artery ligation was performed on day 19 of gestation in Sprague-Dawley pregnant rats. Muscle of the posterior limb was dissected at birth and processed by real-time RTPCR to analyze the expression of insulin receptor, ACCα, ACCβ (acetyl-CoA carboxylase alpha and beta subunits), ACS (acyl-CoA synthase), AMPK (AMP-activated protein kinase, alpha2 catalytic subunit), CPT1B (carnitine palmitoyltransferase-1 beta subunit), MCD (malonyl-CoA decarboxylase) in 14 sham and 8 IUGR pups. Muscle tissue was treated with lysis buffer and Western immunoblotting was performed to assay the protein content of insulin receptor and ACC. Results: A significant down regulation of insulin receptor protein (p < 0.05) and reduced expression of ACS and ACCα mRNA (p < 0.05) were observed in skeletal muscle of IUGR newborns. Immunoblotting showed no significant change in ACCα content. Conclusion: Our data suggest that uteroplacental insufficiency may affect skeletal muscle metabolism down regulating insulin receptor and reducing the expression of key enzymes involved in LCFA formation and oxidation.


Related Articles

  • Hepatic Insulin Resistance Precedes the Development of Diabetes in a Model of Intrauterine Growth Retardation. Vuguin, Patricia; Raab, Elisabeth; Liu, Bing; Barzilai, Nir; Simmons, Rebecca // Diabetes;Oct2004, Vol. 53 Issue 10, p2617 

    Intrauterine growth retardation (IUGR) has been linked to the development of type 2 diabetes in adulthood. We developed an IUGR model in rats whereby at age 3-6 months the animals develop a diabetes that is associated with insulin resistance. Hyperinsulinemic-euglycemic clamp studies were...

  • Postnatal Pancreatic Islet β Cell Function and Insulin Sensitivity at Different Stages of Lifetime in Rats Born with Intrauterine Growth Retardation. Qingxin Yuan; Lu Chen; Cuiping Liu; Kuanfeng Xu; Xiaodong Mao; Chao Liu // PLoS ONE;2011, Vol. 6 Issue 10, p1 

    Epidemiological studies have linked intrauterine growth retardation (IUGR) to the metabolic diseases, consisting of insulin resistance, type 2 diabetes, obesity and coronary artery disease, during adult life. To determine the internal relationship between IUGR and islet β cell function and...

  • Experimental Intrauterine Growth Retardation (IUGR) Induces Global Epigenetic Changes in Rats. Thompson, Reid F.; Simmons, Rebecca A.; Greally, John M.; Barzilai, Nir // Diabetes;Jun2007 Supplement 1, Vol. 56, pA102 

    Uteroplacental insufficiency resulting in intrauterine growth retardation (IUGR) in humans is associated with an increased incidence of type 2 diabetes in adulthood. Rats rendered growth retarded by bilateral uterine artery ligation at 19 days of gestation develop diabetes characterized by...

  • Inactivation of fatty acid transport protein 1 prevents fat-induced insulin resistance in skeletal muscle. Kim, Jason K.; Gimeno, Ruth E.; Higashimori, Takamasa; Hyo-Jeong Kim; Hyejeong Choi; Punreddy, Sandhya; Mozell, Robin L.; Guo Tan, Robin L.; Stricker-Krongrad, Alain; Hirsch, David J.; Fillmore, Jonathan J.; Zhen-Xiang Liu; Jianying Dong; Cline, Gary; Stahl, Andreas; Lodish, Harvey F.; Shulman, Gerald I.; Kim, Hyo-Jeong; Choi, Hyejeong; Tan, Guo // Journal of Clinical Investigation;Mar2004, Vol. 113 Issue 5, p756 

    Insulin resistance in skeletal muscle plays a major role in the development of type 2 diabetes and may be causally associated with increases in intramuscular fatty acid metabolites. Fatty acid transport protein 1 (FATP1) is an acyl-CoA synthetase highly expressed in skeletal muscle and modulates...

  • Associations of apolipoprotein A5 with triglyceride, adiponectin and insulin resistance in patients with impaired glucose regulation and type 2 diabetes mellitus. Yan, Yang; Deng, Huacong; Jian, Long; Su, Yanxin; Li, Yongling; Mi, Gongpu // International Journal of Diabetes in Developing Countries;Mar2013, Vol. 33 Issue 1, p13 

    Hypertriglyceridemia (HTG) is an important feature of lipid metabolism abnormality in patients with type 2 diabetes mellitus (T2DM). Apolipoprotein A5 (apoA5) is positively correlated with triglycerides (TG) and insulin resistance (IR). However, its relationship with TG in humans is still...

  • Genetic variant near IRS1 is associated with type 2 diabetes, insulin resistance and hyperinsulinemia. Rung, Johan; Cauchi, Stéphane; Albrechtsen, Anders; Lishuang Shen; Rocheleau, Ghislain; Cavalcanti-Proença, Christine; Bacot, François; Balkau, Beverley; Belisle, Alexandre; Borch-Johnsen, Knut; Charpentier, Guillaume; Dina, Christian; Durand, Emmanuelle; Elliott, Paul; Hadjadj, Samy; Järvelin, Marjo-Riitta; Laitinen, Jaana; Lauritzen, Torsten; Marre, Michel; Mazur, Alexander // Nature Genetics;Oct2009, Vol. 41 Issue 10, p1110 

    Genome-wide association studies have identified common variants that only partially explain the genetic risk for type 2 diabetes (T2D). Using genome-wide association data from 1,376 French individuals, we identified 16,360 SNPs nominally associated with T2D and studied these SNPs in an...

  • Lack of the architectural factor HMGA1 causes insulin resistance and diabetes in humans and mice. Foti, Daniela; Chiefari, Eusebio; Fedele, Monica; Iuliano, Rodolfo; Brunetti, Leonardo; Paonessa, Francesco; Manfioletti, Guidalberto; Barbetti, Fabrizio; Brunetti, Arturo; Croce, Carlo M.; Fusco, Alfredo; Brunetti, Antonio // Nature Medicine;Jul2005, Vol. 11 Issue 7, p765 

    Type 2 diabetes mellitus is a widespread disease, affecting millions of people globally. Although genetics and environmental factors seem to have a role, the cause of this metabolic disorder is largely unknown. Here we report a genetic flaw that markedly reduced the intracellular expression of...

  • The UPS in diabetes and obesity. Wing, Simon S. // BMC Biochemistry;2008 Supplement 1, Vol. 9, Special section p1 

    Type 2 diabetes is caused by defects in both insulin signaling and insulin secretion. Though the role of the ubiquitin proteasome system (UPS) in the pathogenesis of type 2 diabetes remains largely unexplored, the few examples present in the literature are interesting and suggest targets for...

  • Insulin receptor substrate 1 (IRS1) variants confer risk of diabetes in the Boston Puerto Rican Health Study. Xiang Feng; Tucker, Katherine L.; Parnell, Laurence D.; Jian Shen; Yu-Chi Lee; Ordovás, José M.; Wen-Hua Ling; Chao-Qiang Lai // Asia Pacific Journal of Clinical Nutrition;Mar2013, Vol. 22 Issue 1, p150 

    Objective: Published data concerning associations between 1RS1 variants and type 2 diabetes and related traits have been inconsistent. We examined the relationship between common variants in IRS1, type 2 diabetes, and related traits including insulin resistance, hyperglycemia and DNA damage in...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics