Regulation of pancreatic beta-cell number and function by adipocyte-released hormones, free fatty acids and ghrelin.

糖尿病包括一组以高血糖水平为特征的异质性疾病。胰腺中分泌胰岛素的β细胞是这种疾病的病理生理学中心。1型或胰岛素依赖型糖尿病是由于胰岛β细胞自身免疫破坏导致胰岛素绝对不足所致，占糖尿病总数的5%-10%。在更常见的2型糖尿病或非胰岛素依赖型糖尿病中，肝脏、肌肉和脂肪细胞对胰岛素的作用具有抵抗力，β细胞中激活的增加胰岛素分泌的代偿机制不足以维持正常的血糖水平。在包括澳大利亚在内的西方国家，2型糖尿病目前影响着大约2%的总人口和大约6%的成年人(60岁以上的人中有10%)，并继续以每年约6%的速度增长。2型糖尿病通常发生在肥胖患者中，迄今为止的研究强烈表明肥胖和2型糖尿病之间存在直接联系。还发现，在整个疾病过程中，β细胞功能的进行性丧失会导致胰岛素分泌的减少。肥胖患者过多的脂肪组织在2型糖尿病进展中的作用尚不清楚。脂肪细胞中的某些激素、代谢调节激素和脂肪酸已经在以前的研究中被证明影响β细胞的功能，包括我们自己的研究。我们现在的目标是用分子和细胞生物学技术详细研究这些物质对培养的β细胞的影响。我们期望确定刺激或抑制β细胞功能障碍进展的一个或多个因素，并有可能确定治疗2型糖尿病的靶点。

The disease diabetes mellitus comprises a heterogeneous group of disorders all characterised by high blood glucose levels. Beta-cells in the pancreas, which secrete insulin, are central to the pathophysiology of the disease. Type 1 or insulin-dependent diabetes mellitus results from an absolute deficiency of insulin due to auto immunological destruction of the pancreatic beta cell, and accounts for 5-10% of total diabetes mellitus. In the more common type 2 or non-insulin-dependent diabetes mellitus, liver, muscle and fat cells are resistant to the action of insulin and compensatory mechanisms that are activated in the beta-cell to increase insulin secretion are not sufficient to maintain normal blood glucose levels. In Western countries including Australia, type 2 diabetes currently affects around 2% of the whole population and about 6% of adults (10% of over 60-y) and continues to grow at around 6% per annum. Type 2 diabetes often occurs in obese patients and a direct link between obesity and type 2 diabetes has been strongly suggested by research to date. It has also been found that a progressive loss of beta-cell function throughout the course of the disease results in the reduction of insulin secretion. The contribution of excessive fat tissue in obese patients to the progress of type 2 diabetes is not clear. Certain hormones from fat cells, metabolic regulatory hormone, and fatty acids have been demonstrated to influence the function of beta-cells in previous studies, including our own. We now aim to investigate in detail the effect of these on cultured beta-cells with molecular and cell biology techniques. We expect to identify a factor or factors which stimulate or inhibit the progress of beta-cell dysfunction, with the potential to identify therapeutic targets in the treatment of type 2 diabetes.