Glucose homeostasis is regulated primarily by the opposing actions of insulin and glucagon, hormones that are secreted by pancreatic islets from beta-cells and alpha-cells, respectively. Insulin secretion is increased in response to elevated blood glucose to maintain normoglycemia by stimulating glucose transport in muscle and adipocytes and reducing glucose production by inhibiting gluconeogen...

BACKGROUND Administration of small, intermittent doses of glucagon during closed-loop insulin delivery markedly reduces the frequency of hypoglycemia. However, in some cases, hypoglycemia occurs despite administration of glucagon in this setting. METHODS Fourteen adult subjects with type 1 diabetes participated in 22 closed-loop studies, duration 21.5±2.0 h. The majority of subjects completed...

The effects of insulin and glucagon on the (Na+-K+)-ATPase transport activity in freshly isolated rat hepatocytes were investigated by measuring the ouabain-sensitive, active uptake of 86Rb+. The active uptake of 86Rb+ was increased by 18% (p less than 0.05) in the presence of 100 nM insulin, and by 28% (p less than 0.005) in the presence of nM glucagon. These effects were detected as early as ...

Type 2 diabetes is characterized by an approximately 60% loss of beta-cell mass, a marked defect in postprandial insulin secretion, and a failure to suppress postprandial glucagon concentrations. It is possible that postprandial hyperglucagonemia in type 2 diabetes is due to impaired postprandial insulin secretion. To address this, we studied eight adult Goettingen minipigs before and after an ...

BACKGROUND This study aimed to evaluate the effect of sitagliptin, an oral dipeptidyl peptidase-4 inhibitor, on insulin secretion and glucagon suppression in Korean subjects with type 2 diabetes mellitus. METHODS Twenty-four subjects underwent a 75-g oral glucose tolerance test (OGTT) before and after 6 months of sitagliptin treatment. Sitagliptin, insulin, and sulfonylurea were withdrawn for...

The effect of intrajugular injections of insulin, glucagon and propionate, administered singly and in combination, as possible peripheral feedbacks in the control of feed intake in wethers was studied. A complete mixed diet (25% chopped hay: 75% cracked corn) was fed ad libitum. The treatments were saline, 6 mU insulin/kg body weight (BW), 9 ng glucagon/kg BW and 1.3 mg propionate/kg BW. In Exp...

As successful generation of insulin-producing cells could be used for diabetes treatment, a concerted effort is being made to understand the molecular programs underlying islet beta-cell formation and function. The closely related MafA and MafB transcription factors are both key mammalian beta-cell regulators. MafA and MafB are co-expressed in insulin+beta-cells during embryogenesis, while in t...

The effects of endogenous and exogenous hyperglucagonemia on the specific binding of glucagon to hepatocyte receptors was studied, as was the response of cAMP to glucagon. In streptozotocin diabetic rats, blood glucose and plasma glucagon increased and plasma insulin decreased as compared with controls. Insulin treatment in diabetic rats restored blood glucose and plasma glucagon toward normal ...

Insulin monotherapy can neither maintain normoglycemia in type 1 diabetes (T1D) nor prevent the long-term damage indicated by elevated glycation products in blood, such as glycated hemoglobin (HbA1c). Here we find that hyperglycemia, when unaccompanied by an acute increase in insulin, enhances itself by paradoxically stimulating hyperglucagonemia. Raising glucose from 5 to 25 mM without insulin...

Since the discovery of glucagon’s opposing actions to insulin, drugs targeting the inhibition of glucagon action have been pondered. In recent years, several attempts to generate small molecules or antibodies that impair glucagon action have been pursued as potential therapeutics for type 2 diabetes. In the current issue of Diabetes Care, Kazda et al. (1) summarize the outcomes of the phase 2a ...