Interaction of B0AT1 deficiency and diet on metabolic function and diabetes incidence in male NOD mice.

Context: The obesity epidemic parallels an increasing type 1 diabetes incidence, such that westernized diets, containing high fat, sugar and/or protein, through inducing nutrient-induced islet beta-cell stress, have been proposed as contributing factors. The broad-spectrum neutral amino acid transporter (B0AT1), encoded by Slc6a19, is the major neutral amino acids transporter in intestine and kidney. B0AT1 deficiency in C567Bl/6J mice, causes aminoaciduria, lowers insulinemia and improves glucose tolerance.

High Dietary Iron in Western Diet-Fed Male Rats Causes Pancreatic Islet Injury and Acute Pancreatitis.

Background: High dietary iron has been linked to an increased type 2 diabetes risk. We have previously shown that intrauterine growth restriction (IUGR) and feeding a Western diet (WD) to male Sprague-Dawley rats independently, as well as together, cause pancreatic islet inflammation, fibrosis, and hemosiderosis.

Objectives: To investigate whether iron has a role in the pathogenesis of this inflammatory islet injury caused by IUGR and WD intake.

XBP1 maintains beta cell identity, represses beta-to-alpha cell transdifferentiation and protects against diabetic beta cell failure during metabolic stress in mice.

Aims/hypothesis: Pancreatic beta cell dedifferentiation, transdifferentiation into other islet cells and apoptosis have been implicated in beta cell failure in type 2 diabetes, although the mechanisms are poorly defined. The endoplasmic reticulum stress response factor X-box binding protein 1 (XBP1) is a major regulator of the unfolded protein response. XBP1 expression is reduced in islets of people with type 2 diabetes, but its role in adult differentiated beta cells is unclear.

The Role of Fatty Acid Signaling in Islet Beta-Cell Adaptation to Normal Pregnancy.

Background: Maintenance of a normal fetal nutrient supply requires major adaptations in maternal metabolic physiology, including of the islet beta-cell. The role of lipid signaling processes in the mechanisms of islet beta-cell adaptation to pregnancy has been minimally investigated.

Objective: To determine the effects of pregnancy on islet fatty acid (FA) metabolic partitioning and FA augmentation of glucose-stimulated insulin secretion (GSIS).

Knockout of the Amino Acid Transporter SLC6A19 and Autoimmune Diabetes Incidence in Female Non-Obese Diabetic (NOD) Mice.

High protein feeding has been shown to accelerate the development of type 1 diabetes in female non-obese diabetic (NOD) mice. Here, we investigated whether reducing systemic amino acid availability via knockout of the gene encoding the system B(0) neutral amino acid transporter AT1 would reduce the incidence or delay the onset of type 1 diabetes in female NOD mice. gene deficient NOD mice were generated using the CRISPR-Cas9 system which resulted in marked aminoaciduria.