In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion.

Dysfunctional insulin secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving insulin secretion and lowering blood glucose.

A systematic review of urinary bladder hypertrophy in experimental diabetes: Part 2. Comparison of animal models and functional consequences.

Aims: To explore whether the bladder hypertrophy consistently seen in rats upon streptozotocin injection also occurs in other animal models of type 1 or 2 diabetes and how hypertrophy is linked to functional alterations of the urinary bladder.

Methods: A systematic search for the key word combination "diabetes," "bladder," and "hypertrophy" was performed in PubMed; additional references were identified from reference lists of those publications. All papers were systematically extracted for relevant information.

A systematic review of urinary bladder hypertrophy in experimental diabetes: Part I. Streptozotocin-induced rat models.

Aims: To better understand the genesis and consequences of urinary bladder hypertrophy in animal models of diabetes. This part of a three-article series will analyze urinary bladder hypertrophy in the diabetes mellitus type 1 model of rats injected with streptozotocin (STZ).

Methods: A systematic search for the key word combination "diabetes," "bladder" and "hypertrophy" was performed in PubMed; additional references were identified from reference lists of those publications.

Pancreatic α-cell mass in obesity.

While it is well recognized that obesity is associated with an increased β-cell mass, the association with α-cell mass is less clear. Type 2 diabetes (T2DM) associated with obesity is a bihormonal disease characterized by inadequate insulin secretion and hyperglucagonaemia. We examined β- and α-cell mass throughout the pancreas in obese and lean subjects.

Loss of β-Cell Identity Occurs in Type 2 Diabetes and Is Associated With Islet Amyloid Deposits.

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.

Chronic hyperglycemia downregulates GLP-1 receptor signaling in pancreatic β-cells via protein kinase A.

Objective: Glucagon-like peptide 1 (GLP-1) enhances insulin secretion and protects β-cell mass. Diabetes therapies targeting the GLP-1 receptor (GLP-1R), expressed in numerous tissues, have diminished dose-response in patients with type 2 diabetes compared with healthy human controls. The aim of this study was to determine the mechanistic causes underlying the reduced efficacy of GLP-1R ligands.

PKA Enhances the Acute Insulin Response Leading to the Restoration of Glucose Control.

Diabetes arises from insufficient insulin secretion and failure of the β-cell mass to persist and expand. These deficits can be treated with ligands to Gs-coupled G-protein-coupled receptors that raise β-cell cAMP. Here we studied the therapeutic potential of β-cell cAMP-dependent protein kinase (PKA) activity in restoring glucose control using β-caPKA mice.

Long-term ketogenic diet causes glucose intolerance and reduced β- and α-cell mass but no weight loss in mice.

High-fat, low-carbohydrate ketogenic diets (KD) are used for weight loss and for treatment of refractory epilepsy. Recently, short-time studies in rodents have shown that, besides their beneficial effect on body weight, KD lead to glucose intolerance and insulin resistance. However, the long-term effects on pancreatic endocrine cells are unknown.

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

Aims: Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice.

β-Cell Generation: Can Rodent Studies Be Translated to Humans?

β-cell replacement by allogeneic islet transplantation is a promising approach for patients with type 1 diabetes, but the shortage of organ donors requires new sources of β cells. Islet regeneration in vivo and generation of β-cells ex vivo followed by transplantation represent attractive therapeutic alternatives to restore the β-cell mass. In this paper, we discuss different postnatal cell types that have been envisaged as potential sources for future β-cell replacement therapy.