Glycaemic control and hypoglycaemia benefits with insulin glargine 300 U/mL extend to people with type 2 diabetes and mild-to-moderate renal impairment.

Aim: To investigate the impact of renal function on the safety and efficacy of insulin glargine 300 U/mL (Gla-300) and insulin glargine 100 U/mL (Gla-100).

Materials And Methods: A meta-analysis was performed using pooled 6-month data from the EDITION 1, 2 and 3 trials (N = 2496). Eligible participants, aged ≥18 years with a diagnosis of type 2 diabetes (T2DM), were randomized to receive once-daily evening injections of Gla-300 or Gla-100.

Beta-cell selective K(ATP)-channel activation protects beta-cells and human islets from human islet amyloid polypeptide induced toxicity.

Background And Aims: In type 2 diabetes mellitus (T2DM) chronic beta-cell stimulation and oligomers of aggregating human islet amyloid polypeptide (h-IAPP) cause beta-cell dysfunction and induce beta-cell apoptosis. Therefore we asked whether beta-cell rest prevents h-IAPP induced beta-cell apoptosis.

Materials And Methods: We induced beta-cell rest with a beta-cell selective K(ATP)-channel opener (K(ATP)CO) in RIN cells and human islets exposed to h-IAPP versus r-IAPP.

Annexin A5 directly interacts with amyloidogenic proteins and reduces their toxicity.

Protein misfolding is a central mechanism for the development of neurodegenerative diseases and type 2 diabetes mellitus. The accumulation of misfolded alpha-synuclein protein inclusions in the Lewy bodies of Parkinson's disease is thought to play a key role in pathogenesis and disease progression. Similarly, the misfolding of the beta-cell hormone human islet amyloid polypeptide (h-IAPP) into toxic oligomers plays a central role in the induction of beta-cell apoptosis in the context of type 2 diabetes.

Therapeutic approaches based on beta-cell mass preservation and/or regeneration.

Beta-cell deficiency is a pathophysiologic component of diabetes mellitus and a primary cause of islet dysfunction. Islet dysfunction is a prerequisite for the development of diabetes mellitus since individuals with insulin resistance (e.g.

Impaired islet turnover in human donor pancreata with aging.

Objective: The prevalence of type 2 diabetes mellitus escalates with aging although beta-cell mass, a primary parameter of beta-cell function, is subject to compensatory regulation. So far it is unclear whether the proliferative capacity of pancreatic islets is restricted by senescence.

Materials And Methods: Human pancreatic tissue from n=20 non-diabetic organ donors with a mean age of 50.

Comparison of pancreas-transplanted type 1 diabetic patients with portal-venous versus systemic-venous graft drainage: impact on glucose regulatory hormones and the growth hormone/insulin-like growth factor-I axis.

Context: Pancreas grafts can be drained through the iliac vein (systemic drainage) or the portal vein.

Objective: We hypothesized that normalization of portal insulin in patients with portal pancreas graft drainage stimulates the GH/IGF-I axis and thereby contributes to glucose control.

Methods: We compared patients after combined kidney and pancreas transplantation with portal drainage (n = 7) to patients with systemic drainage of the pancreas graft (n = 8) and nondiabetic controls (n = 8).

Proliferation of colo-357 pancreatic carcinoma cells and survival of patients with pancreatic carcinoma are not altered by insulin glargine.

Objective: It was reported that the long-acting insulin analogue glargine induces cell proliferation in a human osteosarcoma cell line and therefore might induce or accelerate tumor growth. Induction of cell proliferation would be particularly relevant for insulin treatment of subjects with diabetes and the potential of bearing tumor cells (e.g.

Diagnosis and localization of insulinoma after negative laparotomy by hyperinsulinemic, hypoglycemic clamp and intra-arterial calcium stimulation.

A 40-year-old woman with recurrent episodes of hypoglycemia was referred because of suspected insulinoma. Prolonged fasting was discontinued after 24 h due to symptomatic hypoglycemia (29 mg/dl, glucose/insulin-ratio 0.34).

Human islet amyloid polypeptide oligomers disrupt cell coupling, induce apoptosis, and impair insulin secretion in isolated human islets.

Insulin secretion from the 2,000-3,000 beta-cells in an islet is a highly synchronized activity with discharge of insulin in coordinate secretory bursts at approximately 4-min intervals. Insulin secretion progressively declines in type 2 diabetes and following islet transplantation. Both are characterized by the presence of islet amyloid derived from islet amyloid polypeptide (IAPP).

Pancreatic beta-cells secrete insulin in fast- and slow-release forms.

Insulin vesicles contain a chemically rich mixture of cargo that includes ions, small molecules, and proteins. At present, it is unclear if all components of this cargo escape from the vesicle at the same rate or to the same extent during exocytosis. Here, we demonstrate through real-time imaging that individual rat and human pancreatic beta-cells secrete insulin in heterogeneous forms that disperse either rapidly or slowly.

Induction of beta-cell rest by a Kir6.2/SUR1-selective K(ATP)-channel opener preserves beta-cell insulin stores and insulin secretion in human islets cultured at high (11 mM) glucose.

In health, most insulin is secreted in pulses. Type 2 diabetes mellitus (TTDM) is characterized by impaired pulsatile insulin secretion with a defect in insulin pulse mass. It has been suggested that this defect is partly due to chronic overstimulation of beta-cells imposed by insulin resistance and hyperglycemia, which results in depletion of pancreatic insulin stores.

Replication increases beta-cell vulnerability to human islet amyloid polypeptide-induced apoptosis.

Type 2 diabetes is characterized by a relative beta-cell deficit as a result of increased beta-cell apoptosis and islet amyloid derived from the beta-cell peptide islet amyloid polypeptide (IAPP). Human IAPP (h-IAPP) but not mouse IAPP (m-IAPP) induces apoptosis when applied to cells in culture, a property that depends on the propensity of h-IAPP to oligomerize. Since beta-cell mass is regulated, the question arises as to why it is not adaptively increased in response to insulin resistance and hyperglycemia in type 2 diabetes.

Glucose stimulates pulsatile insulin secretion from human pancreatic islets by increasing secretory burst mass: dose-response relationships.

Insulin is secreted almost exclusively in discrete bursts, and physiological regulation is accomplished by modulation of the pulse mass. How the integrity of contiguous anatomic structures in the human pancreas (islets, splanchnic innervation, exocrine tissue, local hormones) directs the coordinated insulin secretion is not known. We posed the hypothesis that glucose stimulates insulin secretion from isolated human islets by an amplification of insulin pulse mass with no change in pulse frequency and that the glucose dose-response curve for the regulation of insulin pulse mass mirrors that recognized in vivo.