As individuals age, the occurrence of diabetes increases, and it is estimated that within the next 15 years, 82 million patients with type 2 diabetes (T2D) in developed countries will be aged 65 years [1]. Caution should be exercised when choosing therapy for T2D in older patients because of comorbidities such as renal impairment, neuropathy and cognitive dysfunc- tion, and treatment regimens, when instituted, should take into consideration the risks of hypoglycaemia, heart failure, renal dysfunction, bone fractures and drug interactions [2,3]. Func- tional impairments, including cognitive decline, peripheral neuropathy, vision and hearing impairments, muscle atrophy, poor posture and balance problems, should also be taken into account when choosing a treatment option [4–10]. Amongst all these concerns, however, prevention of hypoglycaemia is the most important because the consequences of low blood glucose Insulin is a 51 amino acid anabolic peptide-hormone that is secreted by the β-cells in the Islets of Langerhans. Insulin consists of two chains (A and B) connected by disulfide bonds. One of its primary functions is the stimulation of glucose uptake from the systemic circulation, as well as the suppression of hepatic gluconeogenesis, thereby serving a primary role in glucose homeostasis and preventing the metabolic disorder diabetes mellitus 123456. Diabetes is characterized by decreased glucose tolerance resulting from a relative deficiency of insulin or a lack of sensitivity to the endogenous hormone. Insufficient insulin, or decreased insulin sensitivity, results in hypergycemia which is associated with the development of complications such as vascular disease, particularly coronary heart disease, cerebrovascular disease, and the characteristic retinopathy, nephropathy, and neuropathy of this disorder 7. It was Von Mering and Minkowski that first noted that removal of the pancreas led to the development of diabetes mellitus in dogs 8. However it was Schafer in 1916 that first speculated that the antidiabetic hormone, which he decided to call “insuline,” was from the pancreatic islets 9. Barron noted in 1920 that ligation of the pancreatic duct, with destruction of the exocrine pancreas, only resulted in diabetes if the islets, named by Dr. Langerhans in 1869 10, were also destroyed 11. Subsequently, the work of Banting, Best, Collip and MacCleod in the early 1920's resulted in the identification of a substance in extracts of pancreas that had the remarkable ability to reduce blood glucose levels in diabetic animals 1213; and by 1923 these pancreas extracts were being used to successfully treat diabetic patients. Insulin regulates a host of other cellular processes, such as protein and fat synthesis, RNA and DNA synthesis, as well as cell growth and differentiation. It is, however, the regulation of glucose uptake that is of primary concern in the clinical manifestations of diabetes; therefore, this chapter will begin with a brief description of how plasma glucose homeostasis is achieved. inducing tissue-specific genetic alterations under temporal control allows for the analysis of gene function in particular cell types at specified points in time. We have generated a system for tetracycline-controlled expression of Cre recombinase in mice using the unique CreTeR vector. The gonadotroph-specific bovinea-subunit (Ba) promoter fragment was subcloned into the CreTeR vector, creating a technique for highly regulated expression of Cre recombinase exclusively in pituitary gonadotrophs. Control of Cre recombinase in the CreTeR vector was demonstrated in LbT pituitary cell lines, where Cre protein was detected in cells treated with doxycycline, but not in untreated cells. In transgenic mice, Cre was expressed in pituitary gonadotrophs of mice treated with doxycycline, but not in non-pituitary tissues or in transgenic mice not treated with doxycycline. We demonstrated Cre expression in the gonadotroph by immunostaining showing co-localization of Cre recombinase with the b-subunit of LH (LH-b). Furthermore, by crossing Ba/CreTeR with R26R mice, we were able to demonstrate functional recombination within pituitary gonadotrophs, detected by lacZ expression. The Ba /CreTeR mice described here can be used to study the function of virtually any gene in the gonadotroph; inparticular, this will be useful in studying genes, which may have distinct roles in development and in the adult. [GlyB24]insulin is a novel insulin analog which maintains nearly full biological activity [Mirmira, R. G., & Tager, H. S. (1989) J. Biol. Chem. 264, 6349−6354] even though its structure, as determined by 2D NMR, shows complete loss of the characteristic B-chain β-turn [Hua, Q. X., Shoelson, S. E., Kochoyan, M., & Weiss, M. A. (1991) Nature 354, 238−241], which in native insulin allows the extended B-chain C-terminal region to fold against the central B-chain helix. In these studies, steady-state anisotropy measurements and fluorescence quenching analysis of the tryptophan-substituted analogs [TrpB25]insulin and [GlyB24,TrpB25]insulin have been used to study the structure of the C-terminal region of the B-chain and have demonstrated that..... SAMPLE TEXT IS NOT AVAILABLE FOR THIS ARTICLE PLEASE SELECT THE LINK BELOW TO VIEW FULL ARTICLE! Gonadotrophin-releasing hormone (GnRH) neurones located within the brain are the final neuroendocrine output regulating the reproductive hormone axis. Their small number and scattered distribution in the hypothalamus make them particularly difficult to study in vivo. The Cre/loxP system is a valuable tool to delete genes in specific cells and tissues. We report the production of two mouse lines that express the CRE bacteriophage recombinase in a GnRH-specific manner. The first line, the GnRH-CRE mouse, contains a transgene in which CRE is under the control of the murine GnRH promoter and targets CRE expression specifically to GnRH neurones in the hypothalamus.