Protocatechualdehyde restores endothelial dysfunction in streptozotocin-induced diabetic rats.

Background: The present study was conducted with the aim of clarifying the effects of protocatechualdehyde (PCA) on the endothelial function in streptozotocin (STZ)-induced diabetic rats.

Methods: Sprague Dawley (SD) rats were intraperitoneally injected with STZ (single dose of 60 mg/kg). Diabetic model rats were given PCA (25 mg/kg/day) via gavage feeding for 6 weeks.

Irisin Is a Positive Regulator for Ferroptosis in Pancreatic Cancer.

Regulated cell death by way of ferroptosis involves iron-dependent accumulation of cellular reactive oxygen species (ROS). Ferroptosis is attracting attention as a potential therapeutic target for cancer treatments without drug resistance. The relationship between irisin, a myokine involved in autophagy and ROS metabolism, and ferroptosis is unclear.

Erastin-induced ferroptosis is a regulator for the growth and function of human pancreatic islet-like cell clusters.

Ferroptosis is a newly identified and novel form of cell death, which is characterized by an iron- and reactive oxygen species (ROS)-dependent manner. Potential utility of ferroptotic cell death has been recently proposed for cancer treatment. Meanwhile, ROS generation and apoptosis are inherently consequent to cell apoptosis and dysfunction during islet cell preparation and transplantation.

Alcohol ingestion induces pancreatic islet dysfunction and apoptosis via mediation of FGF21 resistance.

Background: Disruption of β-cell insulin secretion and viability caused by excessive ethanol consumption increases type 2 diabetes mellitus (T2DM) pathogenesis risk. Fibroblast growth factor 21 (FGF21) plays a significant role in regulating lipid and glucose homeostasis. Recently, FGF21, best known for its role in lipid and glucose homeostasis regulation, and its obligate co-receptor β-klotho have been shown to inhibit ethanol ingestion and metabolism.

Fibroblast growth factor 21 protects against lipotoxicity-induced pancreatic β-cell dysfunction via regulation of AMPK signaling and lipid metabolism.

Fibroblast growth factor 21 (FGF21) is known as a potent metabolic regulator but its protective mechanisms against lipotoxicity-induced β-cell dysfunction and apoptosis remain elusive. Here, we aimed to examine the regulatory pathways whereby FGF21 mediates islet lipid metabolism in lipotoxicity-treated cells and animal models. Rat β-cell line (INS-1E cells) and islets isolated from C57/BL6J mice were exposed to palmitic acid (PA) with/without FGF21, mimicking lipotoxic conditions.

SIRT1 Activation Promotes β-Cell Regeneration by Activating Endocrine Progenitor Cells via AMPK Signaling-Mediated Fatty Acid Oxidation.

Induction of β-cell regeneration from endogenous cells represents a highly promising strategy in stem cell-based treatment for patients with diabetes. Recently, calorie restriction has been shown to affect the regulation of tissue and cell regeneration, including β cells, via metabolic related mechanisms. Here, we examined the potential utility of sirtuin 1 (SIRT1), a calorie restriction mimetic, for stimulating β-cell regeneration and the underlying mechanisms of such stimulation.

The Modulatory Action of Vitamin D on the Renin-Angiotensin System and the Determination of Hepatic Insulin Resistance.

Vitamin D deficiency or hypovitaminosis D is associated with increased risks of insulin resistance, type 2 diabetes mellitus (T2DM) and its related non-alcoholic fatty liver disease (NAFLD). Meanwhile, inappropriate over-activation of the renin-angiotensin system (RAS) in the liver leads to the hepatic dysfunction and increased risk of T2DM, such as abnormalities in lipid and glucose metabolism. Our previous findings have shown that calcitriol, an active metabolite of vitamin D, reduces hepatic triglyceride accumulation and glucose output in diabetic db/db mice and human hepatocellular cell HepG2 cells under insulin-resistant conditions.

Fibroblast Growth Factor 21 Stimulates Pancreatic Islet Autophagy via Inhibition of AMPK-mTOR Signaling.

Background: Islet autophagy plays a role in glucose/lipid metabolism in type 2 diabetes mellitus. Meanwhile, fibroblast growth factor 21 (FGF21) has been found to regulate insulin sensitivity and glucose homeostasis. Whether FGF21 induces islet autophagy, remains to be elucidated.

GPR120 protects lipotoxicity-induced pancreatic β-cell dysfunction through regulation of PDX1 expression and inhibition of islet inflammation.

G-protein coupled receptor 120 (GPR120) has been shown to act as an omega-3 unsaturated fatty acid sensor and is involved in insulin secretion. However, the underlying mechanism in pancreatic β cells remains unclear. To explore the potential link between GPR120 and β-cell function, its agonists docosahexaenoic acid (DHA) and GSK137647A were used in palmitic acid (PA)-induced pancreatic β-cell dysfunction, coupled with GPR120 knockdown (KD) in MIN6 cells and GPR120 knockout (KO) mice to identify the underlying signaling pathways.

Irisin Ameliorates Glucolipotoxicity-Associated β-Cell Dysfunction and Apoptosis via AMPK Signaling and Anti-Inflammatory Actions.

Background/aims: Islet metabolic disorder and inflammation contribute to the pathogenesis and progression of type 2 diabetes mellitus (T2DM). Irisin is a recently identified adipomyokine with protective effects on metabolic homeostasis and inflammation-suppressing effects in hepatic and vascular cells. The present study examined the effects of irisin on lipid metabolism and inflammation in β cells under glucolipotoxic conditions.

GPR120 is an important inflammatory regulator in the development of osteoarthritis.

Background: The aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA).

Methods: GPR120 knockout (KO) and wild-type (WT) mice were used to create an animal model of OA by means of anterior cruciate ligament transection (ACLT) surgery. The severity of OA was staged and evaluated by histological examination, microcomputed tomography scan and enzyme-linked immunosorbent assay (ELISA).

Brucein D, a Naturally Occurring Tetracyclic Triterpene Quassinoid, Induces Apoptosis in Pancreatic Cancer through ROS-Associated PI3K/Akt Signaling Pathway.

Brucein D (BD), a major active quassinoid in , has exhibited pronounced anticancer activities. However, the biologic mechanisms have not been fully explored. In this study, BD exhibited more potent cytotoxic effect on pancreatic cancer (PanCa) cell lines, while exerted weaker cytotoxic effects on GES-1 cells (non-tumorigenic).

Na /H exchanger 3 blockade ameliorates type 2 diabetes mellitus via inhibition of sodium-glucose co-transporter 1-mediated glucose absorption in the small intestine.

Aim: To elucidate the role of Na /H exchanger 3 (NHE3) in sodium-glucose co-transporter 1 (SGLT1)-mediated small intestinal brush border membrane (BBM) glucose absorption and its functional implications in type 2 diabetes mellitus (T2DM).

Materials And Methods: Human jejunal samples were obtained from patients undergoing gastrectomy. C-glucose absorption was measured by liquid scintillation counting.

Fibroblast growth factor 21: a regulator of metabolic disease and health span.

Fibroblast growth factor 21 (FGF21) is a potent endocrine regulator with physiological effects on glucose and lipid metabolism and thus garners much attention for its translational potential for the management of obesity and related metabolic syndromes. FGF21 is mainly expressed in several metabolically active tissue organs, such as the liver, adipose tissue, skeletal muscle, and pancreas, with profound effects and therapeutic relevance. Emerging experimental and clinical data point to the demonstrated metabolic benefits of FGF21, which include, but are not limited to, weight loss, glucose and lipid metabolism, and insulin sensitivity.

Identification and Functional Implications of Sodium/-Inositol Cotransporter 1 in Pancreatic β-Cells and Type 2 Diabetes.

-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, although the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/-inositol cotransporter 1 (SMIT1) in rat islets and, specifically, β-cells.

Angiotensin II Type 2 Receptor Activation With Compound 21 Augments Islet Function and Regeneration in Streptozotocin-Induced Neonatal Rats and Human Pancreatic Progenitor Cells.

Objectives: We investigated the effects of compound 21 (C21), a nonpeptide angiotensin II type 2 receptor agonist, on islet cell function and survival in streptozotocin (STZ)-treated neonatal rats and human pancreatic progenitor cells.

Methods: Neonatal rats were randomized into 5 groups, including a control, an STZ (100 mg/kg, intraperitoneally), and 3 STZ + C21 (0.25, 0.

Insulinotropic effects of GPR120 agonists are altered in obese diabetic and obese non-diabetic states.

G-protein-coupled receptor 120 (GPR120) is a putative target for obesity and diabetes therapies. However, it remains controversial whether resident GPR120 plays a direct regulatory role in islet β-cell insulin secretion. The present study examined this issue in isolated rodent islets and rat β-cell line INS-1E, and assessed the role of GPR120 in islet insulin secretion in obese non-diabetic (OND) and diabetic states.