Studies in transgenic animals, rodent insulin-secreting cell lines and rodent islets suggest that insulin acts in an autocrine manner to regulate beta-cell mass and gene expression. Very little is known about the in vitro roles played by insulin in human islets, and the regulatory role of insulin in protecting against beta-cell apoptosis. We have identified mRNAs encoding IRs (insulin receptors...

For the majority of patients with type 1 diabetes intensive insulin therapy is effective and safe for maintaining glycemia and minimizing diabetes-associated complications. However, a rare number of patients show highly labile metabolic control and experience repeated and unpredictable hypoglycemic episodes. Such condition is often caused by defective counterregulatory mechanisms and autonomous...

Defects in pancreatic -cell function contribute to the development of type 2 diabetes, a polygenic disease that is characterized by insulin resistance and compromised insulin secretion. Hepatocyte nuclear factors (HNFs) -1 , -3 , -4 , and Pdx-1 contribute in the complex transcriptional circuits within the pancreas that are involved in -cell development and function. In mice, a heterozygous muta...

Potential insulin secretagogue properties of an acetoxymethyl ester of a cAMP analog (8-pCPT-2'-O-Me-cAMP-AM) that activates the guanine nucleotide exchange factors Epac1 and Epac2 were assessed using isolated human islets of Langerhans. RT-QPCR demonstrated that the predominant variant of Epac expressed in human islets was Epac2, although Epac1 was detectable. Under conditions of islet perifus...

Plasma insulin measurements from mice, rats, dogs, and humans indicate that insulin levels are oscillatory, reflecting pulsatile insulin secretion from individual islets. An unanswered question, however, is how the activity of a population of islets is coordinated to yield coherent oscillations in plasma insulin. Here, using mathematical modeling, we investigate the feasibility of a potential i...

Ghrelin has emerged as an important player in the regulation of glucose homeostasis. During caloric restriction, the presence of acyl ghrelin (the active isoform) is necessary for the defense against hypoglycemia and survival [1]. In fasted humans, ghrelin administration enhances growth hormone (GH) secretion, suppresses insulin release and promotes insulin resistance to maintain normoglycemia ...

BACKGROUND Sirolimus (SRL) has been associated with new-onset diabetes mellitus after transplantation. The aim was to determine the effect of SRL on development of insulin resistance and β -cell toxicity. METHODS Lean Zucker rat (LZR) and obese Zucker rat (OZR) were distributed into groups: vehicle and SRL (0.25, 0.5, or 1.0 mg/kg) during 12 or 28 days. Intraperitoneal glucose tolerance test ...

OBJECTIVE Insulin release from pancreatic islet β cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs) by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell ...

Type 2 diabetes is characterized by islet dysfunction resulting in hyperglycemia, which can then lead to further deterioration in islet function. A possible mechanism for hyperglycemia-induced islet dysfunction is the accumulation of advanced glycation end products (AGE). The DBA/2 mouse develops pancreatic islet dysfunction when exposed to a high glucose environment and/or obesity-induced insu...

Several studies have revealed that physiological concentrations of biotin are required for the normal expression of critical carbohydrate metabolism genes and for glucose homeostasis. However, the different experimental models used in these studies make it difficult to integrate the effects of biotin deficiency on glucose metabolism. To further investigate the effects of biotin deficiency on gl...