Studies from the laboratory of Roger Unger presented in the current issue of Diabetes highlight the potential benefit of reducing glucagon action by examining the effects of glucagon receptor knockout (Gcgr) on the phenotype of type 1 diabetes in the mouse (1). The aim of the study was to determine if glucagon action, by itself, causes the lethal consequences of insulin deficiency. Because trea...

AIMS Glucagon-like peptide-1 (GLP-1) receptor agonists improve blood glucose control by enhancing glucose-sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo. METHODS Two single-centre, doubl...

Introduction: Gama amino butyric acid (GABA) is the major inhibitory neurotransmitter in the mammalian nervous system. The concentration of GABA and the number of GABA cell secretion decrease in diabetic patient and experimental diabetes model. The reported effects of GABA activation on insulin secretion from beta cells have been controversial. In this study we investigated if GABA administr...

New results have brought to light the importance of the regulation of glucagon by β-cells in the development of diabetes. In this perspective, we examine the normal paracrinology of α- and β-cells in nondiabetic pancreatic islets. We propose a Sherringtonian model of coordinated reciprocal secretory responses of these juxtaposed cells that secrete glucagon and insulin, hormones with opposing ac...

Emphasis was recently placed on the modulation of glucagon secretion attributable to a paracrine effect of somatostatin. This review draws attention to prior findings related to such a view. The effects of nutrient secretagogues upon insulin, somatostatin and glucagon release by the perfused pancreas are first considered. Three examples of paradoxical secretory responses of insulin- and glucago...

Type 2 diabetes is manifested by impaired insulin secretion in pancreatic beta cells, increased glucagon alpha and generally has a history of resistance. The treatment glucose metabolism disorder the resulting hyperglycemia constitute an important part type diabetes. Glycemic targets can be targeted with A1C

The hyperglucagonemia that occurs in vivo in animals made diabetic with alloxan or streptozotocin is not suppressed by high glucose but is suppressed by exogenous insulin. These observations together with other studies suggested that insulin-dependent glucose transport and metabolism by the alpha-cells serves as the primary mechanism controlling glucagon secretion. This hypothesis was tested in...

BACKGROUND Intra-islet insulin contributes to alpha-cell suppression. Akita mice carry a toxic-gain-of- function Ins2 gene mutation encoding proinsulin-C(A7)Y, similar to that described in human Mutant Ins-gene induced Diabetes of Youth, which decreases intra-islet insulin. Herein, we examined Akita mice for examination of circulating insulin and circulating glucagon levels. The possibility tha...

It is now recognized that the metabolic disorders observed in diabetes are not, or not only due to the lack of insulin or insulin resistance, but also to elevated glucagon secretion. Accordingly, selective glucagon receptor antagonists are now proposed as a novel strategy for the treatment of diabetes. However, besides its metabolic actions, glucagon also influences kidney function. The glucago...

Loss of pancreatic islet β-cell mass and β-cell dysfunction are central in the development of type 2 diabetes (T2DM). We recently showed that mature human insulin-containing β-cells can convert into glucagon-containing α-cells ex vivo. This loss of β-cell identity was characterized by the presence of β-cell transcription factors (Nkx6.1, Pdx1) in glucagon(+) cells. Here, we investigated whether...