Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β-cells.

Both type 2 diabetes (T2D) and obesity are characterized by excessive hyperlipidaemia and subsequent lipid droplet (LD) accumulation in adipose tissue. To investigate whether LDs also accumulate in β-cells of T2D patients, we assessed the expression of PLIN2, a LD-associated protein, in non-diabetic (ND) and T2D pancreata. We observed an up-regulation of PLIN2 mRNA and protein in β-cells of T2D patients, along with significant changes in the expression of lipid metabolism, apoptosis and oxidative stress genes.

Islet Neogenesis Associated Protein (INGAP) induces the differentiation of an adult human pancreatic ductal cell line into insulin-expressing cells through stepwise activation of key transcription factors for embryonic beta cell development.

Regeneration of β-cells in diabetic patients is an important goal of diabetes research. Islet Neogenesis Associated Protein (INGAP) was discovered in the partially duct-obstructed hamster pancreas. Its bioactive fragment, pentadecapeptide 104-118 (INGAP-P), has been shown to reverse diabetes in animal models and to improve glucose homeostasis in patients with diabetes in clinical trials.

Mechanisms of action of islet neogenesis-associated protein: comparison of the full-length recombinant protein and a bioactive peptide.

Islet neogenesis-associated protein (INGAP) was discovered in the partially duct-obstructed hamster pancreas as a factor inducing formation of new duct-associated islets. A bioactive portion of INGAP, INGAP(104-118) peptide (INGAP-P), has been shown to have neogenic and insulin-potentiating activity in numerous studies, including recent phase 2 clinical trials that demonstrated improved glucose homeostasis in both type 1 and type 2 diabetic patients. Aiming to improve INGAP-P efficacy and to understand its mechanism of action, we cloned the full-length protein (rINGAP) and compared the signaling events induced by the protein and the peptide in RIN-m5F cells that respond to INGAP with an increase in proliferation.

Epidermal growth factor induces adult human islet cell dedifferentiation.

Given the inherent therapeutic potential of the morphogenetic plasticity of adult human islets, the identification of factors controlling their cellular differentiation is of interest. The epidermal growth factor (EGF) family has been identified previously in the context of pancreatic organogenesis. We examined the role of EGF in an in vitro model whereby adult human islets are embedded in a collagen gel and dedifferentiated into duct-like epithelial structures (DLS).

Production and characterization of the recombinant Islet Neogenesis Associated Protein (rINGAP).

Islet Neogenesis Associated Protein (INGAP) is implicated in pancreatic islet neogenesis. INGAP peptide, a pentadecapeptide comprising amino acids 104-118, reverses diabetes in rodents and improves glucose homeostasis in patients with diabetes. The mechanism of INGAP action is unknown, but such studies would benefit from the availability of the full-length recombinant protein (rINGAP).

Staphylococcus aureus ArcR controls expression of the arginine deiminase operon.

We identified a single open reading frame that is strongly similar to ArcR, a member of the Crp/Fnr family of bacterial transcriptional regulators, in all sequenced Staphylococcus aureus genomes. The arcR gene encoding ArcR forms an operon with the arginine deiminase (ADI) pathway genes arcABDC that enable the utilization of arginine as a source of energy for growth under anaerobic conditions. In this report, we show that under anaerobic conditions, S.

Development of an in vitro pancreatic tissue model to study regulation of islet neogenesis associated protein expression.

Restoration of a functional beta-cell mass in a patient with diabetes may hold the key for curing the disease. In recent years, there has been increasing interest in the development of new strategies to induce beta-cell regeneration and new islet formation in situ and a role for Reg proteins has been suggested. One such protein, islet neogenesis associated protein (INGAP), is a member of the Reg3 family of proteins and has been shown to induce islet neogenesis.