Diabetes is a disease characterized by a relative or absolute lack of insulin, leading to hyperglycaemia. There are two main types of diabetes: type 1 diabetes and type 2 diabetes. Type 1 diabetes is due to an autoimmune destruction of the insulin-producing pancreatic beta cells, and type 2 diabetes is caused by insulin resistance coupled by a failure of the beta cell to compensate. Animal models for type 1 diabetes range from animals with spontaneously developing autoimmune diabetes to chemical ablation of the pancreatic beta cells. Type 2 diabetes is modelled in both obese and non-obese animal models with varying degrees of insulin resistance and beta cell failure. This review outlines some of the models currently used in diabetes research. In addition, the use of transgenic and knock-out mouse models is discussed. Ideally, more than one animal model should be used to represent the diversity seen in human diabetic patients.

OBJECTIVE-Somatostatin (SST) is secreted by islet ␦-cells and by extraislet neuroendocrine cells. SST receptors have been identified on ␣-and ␤-cells, and exogenous SST inhibits insulin and glucagon secretion, consistent with a role for SST in regulating ␣-and ␤-cell function. However, the specific intraislet function of ␦-cell SST remains uncertain. We have used Sst Ϫ/Ϫ mice to investigate the role of ␦-cell SST in the regulation of insulin and glucagon secretion in vitro and in vivo. RESEARCH DESIGN AND METHODS-Islet morphology wasassessed by histological analysis. Hormone levels were measured by radioimmunoassay in control and Sst Ϫ/Ϫ mice in vivo and from isolated islets in vitro. RESULTS-Islet size and organization did not differ between SstϪ/Ϫ and control islets, nor did islet glucagon or insulin content. Sst Ϫ/Ϫ mice showed enhanced insulin and glucagon secretory responses in vivo. In vitro stimulus-induced insulin and glucagon secretion was enhanced from perifused Sst Ϫ/Ϫ islets compared with control islets and was inhibited by exogenous SST in Sst Ϫ/Ϫ but not control islets. No difference in the switch-off rate of glucose-stimulated insulin secretion was observed between genotypes, but the cholinergic agonist carbamylcholine enhanced glucose-induced insulin secretion to a lesser extent in Sst Ϫ/Ϫ islets compared with controls. Glucose suppressed glucagon secretion from control but not Sst Ϫ/Ϫ islets.CONCLUSIONS-We suggest that ␦-cell SST exerts a tonic inhibitory influence on insulin and glucagon secretion, which may facilitate the islet response to cholinergic activation. In addition, ␦-cell SST is implicated in the nutrient-induced suppression of glucagon secretion. Diabetes 58:403-411, 2009

The pathophysiology of diabetes as a disease is characterised by an inability to maintain normal glucose homeostasis. In type 1 diabetes, this is due to autoimmune destruction of the pancreatic b-cells and subsequent lack of insulin production, and in type 2 diabetes it is due to a combination of both insulin resistance and an inability of the b-cells to compensate adequately with increased insulin release. Animal models, in particular genetically modified mice, are increasingly being used to elucidate the mechanisms underlying both type 1 and type 2 diabetes, and as such the ability to study glucose homeostasis in vivo has become an essential tool. Several techniques exist for measuring different aspects of glucose tolerance and each of these methods has distinct advantages and disadvantages. Thus the appropriate methodology may vary from study to study depending on the desired end-points, the animal model, and other practical considerations. This review outlines the most commonly used techniques for assessing glucose tolerance in rodents and details the factors that should be taken into account in their use. Representative scenarios illustrating some of the practical considerations of designing in vivo experiments for the measurement of glucose homeostasis are also discussed.

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Aims/hypothesis Recent studies have shown that mesenchymal stem cells (MSCs) secrete several factors that improve survival and function of transplanted islets. Implantation of islets beneath the kidney capsule results in morphological changes, due to interactions of the graft with the host, thus impairing islet function. We co-transplanted MSCs with islets to determine their effects on the remodelling process and studied graft function in a mouse model of minimal islet mass. Methods Islets were syngeneically transplanted, either alone or with kidney-derived MSCs, underneath the kidney capsule of streptozotocin-induced diabetic C57Bl/6 mice. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests carried out. Hormone contents of grafts and pancreas were assessed by radioimmunoassay. Graft morphology and vascularisation were evaluated by immunohistochemistry. Results MSCs improved the capacity of islet grafts to reverse hyperglycaemia, with 92% of mice co-transplanted with MSCs reverting to normoglycaemia, compared with 42% of those transplanted with islets alone. Average blood glucose concentrations were lower throughout the 1 month monitoring period in MSC co-transplanted mice. MSCs did not alter graft hormone content. Islets co-transplanted with MSCs maintained a morphology that more closely resembled that of islets in the endogenous pancreas, both in terms of size, and of endocrine and endothelial cell distribution. Vascular engraftment was superior in MSC co-transplanted mice, as shown by increased endothelial cell numbers within the endocrine tissue. Conclusions/interpretation Co-transplantation of islets with MSCs had a profound impact on the remodelling process, maintaining islet organisation and improving islet revascularisation. MSCs also improved the capacity of islets to reverse hyperglycaemia.