Insulin receptors in lizard brain and liver: structural and functional studies of α and β subunits demonstrate evolutionary conservation

Summary Specific insulin receptors are present in the liver and brain of the lizard Anolis carolinesis. In this study, the specific binding of ¹²⁵I-insulin to the receptors showed time, temperature and pH dependency. Specific binding to crude membranes prepared from brain was 1–2% of the total radioactivity added compared to 4–5% in the crude membranes prepared from liver. Solubilization and wheat germ agglutinin purification of the membranes resulted in an increase in the specific binding (per mg of protein) between 6 and 32 times for liver membranes and 13–186 for brain membranes. Binding inhibition of tracer insulin by unlabeled porcine insulin was characteristic for insulin receptors with 50% inhibition for liver crude membranes at 60 ng/ml of porcine insulin and 0.7 ng/ml for purified brain insulin receptors. Chicken insulin was 2- to 3-fold more potent and proinsulin about 100 times less potent than porcine insulin. The -subunits of liver and brain had apparent molecular weights on sodium dodecyl sulfate polyacrylamide gel electrophoresis of 135 kDa and 120 kDa respectively. Apparent molecular weights of subunits were 92 kDa for both tissues. Insulin stimulated phosphorylation of the subunit of both brain and liver receptors. Both tissues demonstrated tyrosine-specific phosphorylation, which was stimulated by insulin, of exogenously added artificial substrates. In addition, purified brain insulin receptor preparations contained an endogenous protein with apparent molecular weight of 105 kDa, whose phosphorylation was stimulated by insulin (10^–7 mol/l). This phosphoprotein was not immunoprecipitated by anti-insulin receptor antibodies. These studies suggest that the structural differences between brain and liver receptors previously demonstrated in the rat are also present in the lizard, which is about 300,000,000 years older than the mammalian species. Thus, there is strong evolutionary conservation of the brain insulin receptor.     

Association of Insulin Resistance and Higher Oncotype DX™ Recurrence Score

Annals of Surgical Oncology - Black women with breast cancer have a worse overall survival compared with White women; however, no difference in Oncotype DX? (ODX) recurrence scores has been...     

Functional insulin-like growth factor I receptors are expressed by neural-derived continuous cell lines

High affinity insulin-like growth factor I (IGF-I) receptors are expressed by two human neural derived cell lines, SK-N-SH and SK-N-MC. Specific [125I]IGF-I binding to crude membranes was 23.4% for SK-N-SH and 10.7% for SK-N-MC, with 50% inhibition of binding by unlabeled IGF-I between 0.6-0.7 nM. Scatchard analysis of crude membrane binding was linear, whereas Scatchard analysis after wheat germ agglutinin purification of the receptor became curvilinear. The IGF-I receptor alpha-subunits of SK-N-SH have an apparent Mr of 126K, whereas that for SK-N-MC is 132K. Despite these differences in alpha-subunit structure both cell lines demonstrate IGF-I-induced autophosphorylation of their own beta-subunits as well as specific IGF-I induced tyrosine kinase activity, suggesting normal coupling between the ligand-binding alpha-subunit and the tyrosine kinase-containing beta-subunit. Furthermore, IGF-I stimulated iododeoxyuridine uptake in both SK-N-SH and SK-N-MC in a dose-dependent manner, suggesting that these cells may be used to study the role of IGF-I action on neural tissues.     

Non-islet cell hypoglycemia

NICTH is a fairly uncommon disorder but has been well characterized and the molecular mechanisms involved have given insights into the IGF system, both normal and abnormal. NICTH has brought together the molecular biologists and endocrinologists in a classic cross cultural coordination to study the disorder from all angles and to further understand the disorder.     

Insulin resistance as the underlying cause for the metabolic syndrome

Classically, the metabolic syndrome is characterized as group of pathologies including visceral obesity, hypertension, dyslipidemia, and impaired glucose tolerance. It is now realized that insulin resistance plays a principal role in initiating and perpetuating the pathologic manifestations of the metabolic syndrome. A more in-depth understanding of the basic pathophysiologic mechanisms underlying insulin resistance may aid clinicians in treating and possibly delaying or even preventing the onset of the metabolic syndrome and its complications. This article outlines how abnormal insulin signaling and secretion, impaired glucose disposal, lipotoxicity, and proinflammatory cytokines exacerbate insulin resistance and result in the perturbations of the metabolic syndrome.     

Overcoming the barriers for achieving standards of diabetes care: the formation of CADRE

Diabetes remains one of the leading causes of death and disability in the United States. Despite significant breakthroughs in treatment of diabetes, recent reports suggest a large number of patients are not at target goals for blood pressure, lipids, and glucose levels. Failure to achieve these goals is most likely not due to the unavailability of drugs and innovations, as numerous drugs have been released over the past 10 years, and monitoring of blood glucose is now considered routine. Therefore, other obstacles must exist at the primary care level preventing adherence to suggested targets. Based on the above, the Council for the Advancement of Diabetes Research and Education (CADRE), a membership organization, was launched in an effort to address the problem of understanding diabetes and its treatment. The ultimate goal of CADRE is to expand understanding of diabetes and its treatment by providing educational programs enabling healthcare professionals to manage and empower patients with diabetes. In particular, by focusing on innovations in diabetes care, CADRE hopes to promote optimal therapy for meeting the treatment goals as outlined by governing bodies such as the American Diabetes Association. This article will focus on the formation of CADRE, and, in particular, identification of the problem contributing to the obstacles of care, and review various surveys conducted by CADRE designed in an effort to identify the problem.     

Insulin and IGF-1 induce different patterns of gene expression in mouse fibroblast NIH-3T3 cells: identification by cDNA microarray analysis

The IGF-1 receptor and the related insulin receptor are similar in structure and activate many of the same postreceptor signaling pathways, yet they mediate distinct biological functions. It is still not understood how the specificity of insulin vs. IGF-1 signaling is controlled. In this study, we have used cDNA microarrays to monitor the gene expression patterns that are regulated by insulin and IGF-1. Mouse fibroblast NIH-3T3 cells expressing either the wild-type human IGF receptor or the insulin receptor were stimulated with either IGF-1 or insulin, respectively. Thirty genes, 27 of which were not previously known to be IGF-1 responsive, were up-regulated by IGF-1 but not by insulin. Nine genes, none of which was previously known to be insulin responsive, were up-regulated by insulin but not by IGF-1. The IGF- and insulin-induced regulation of 10 of these genes was confirmed by Northern blot analysis. Interestingly, more than half of the genes up-regulated by IGF-1 are associated with mitogenesis and differentiation, whereas none of the genes specifically up-regulated by insulin are associated with these processes. Our results indicate that under the conditions used in this study, IGF-1 is a more potent activator of the mitogenic pathway than insulin in mouse fibroblast NIH-3T3 cells.