Ins-1

Target identification is a crucial step in elucidating the mechanisms by which functional food components exert their functions. Here, we identified the G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) as a target of the triterpenoid mogrol, a class of aglycone mogroside derivative from Siraitia grosvenorii. Mogrol, but not mogrosides, activated cAMP-response element-mediated transcription in a TGR5-dependent manner. Additionally, mogrol selectively activated TGR5 but not the other bile acid-responsive receptors (i...

Dairy cows with clinical ketosis (CK) exhibit excessive adipose tissue (AT) lipolysis and systemic inflammation. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory lipolytic pathways. Currently, the most common treatment for CK is oral propylene glycol (PG); however, PG does not reduce lipolysis or inflammation. Niacin (NIA) can reduce the activation of canonical lipolysis, whereas cyclooxygenase inhibitors such as flunixin meglumine (FM) can limit inflammation and inhibit the inflammatory lipolytic pathway...

Biomedical devices such as islet-encapsulating systems are used for treatment of type 1 diabetes (T1D). Despite recent strides in preventing biomaterial fibrosis, challenges remain for biomaterial scaffolds due to limitations on cells contained within. The study demonstrates that proliferation and function of insulinoma (INS-1) cells as well as pancreatic rat islets may be improved in alginate hydrogels with optimized gel%, crosslinking, and stiffness. Quantitative polymerase chain reaction (qPCR)-based graft phenotyping of encapsulated INS-1 cells and pancreatic islets identified a hydrogel stiffness range between 600 and 1000 Pa that improved insulin Ins and Pdx1 gene expression as well as glucose-sensitive insulin-secretion...

OBJECTIVES: This study focused on the evaluation of antioxidant and antidiabetic activities of polyherbal extract (PHE), containing Cassia absus (L.), Gymnema sylvestre (R. Br.), Nigella sativa (L.), and Piper nigrum (L.), in alloxan-induced diabetes model. MATERIALS AND METHODS: In vitro , HPLC characterization, DPPH scavenging assay, and α-amylase inhibition test were conducted. In vivo , acute oral toxicity of PHE was assessed. Alloxan-induced diabetic Wistar rats (n=6) were orally treated with PHE (200, 400, and 600 mg/kg/day) and glibenclamide (GLB; 10 mg/kg/day) for six consecutive weeks...

AIMS: In this study, we investigated the role of the FTO gene in pancreatic β-cell biology and its association with type 2 diabetes (T2D). To address this issue, human pancreatic islets and rat INS-1 (832/13) cells were used to perform gene silencing, overexpression, and functional analysis of FTO expression; levels of FTO were also measured in serum samples obtained from diabetic and obese individuals. RESULTS: The findings revealed that FTO expression was reduced in islets from hyperglycemic/diabetic donors compared to normal donors...

Insulinoma is a neuroendocrine tumor. It arises from the uncontrolled proliferation of pancreatic β cells. In this study, we created an insulinoma tumor model in nude mice. INS-1 cells were injected in two different ways, subcutaneously (S.C.) or intraperitoneally (I.P.). Body weight, tumor weight, and size were measured. ELISA kits were used analyze to Glucose, insulin, and CA19-9 levels in serum, pancreas, and tumor tissues. KCNN4, KCNK1, GLUT2, IR, HSP70, HSF1, and HSP90 levels were analyzed by western blotting of membrane and/or cytosolic fractions of tumor and pancreas tissue...

BACKGROUND: Roux-en-Y gastric bypass surgery (RYGB) improves glucose-stimulated insulin secretion (GSIS) in type 2 diabetes (T2D) patients. SNAP25 plays an essential role in GSIS. Clinical studies indicate that enhanced GLP-1 signaling is an important contributor to the improved β-cell function in T2D. We aimed to explore whether GLP-1-regulated SNAP25 is involved in the enhanced secretory function of β-cells in diabetic Goto-Kakizaki (GK) rats after RYGB. METHODS AND RESULTS: RYGB or sham surgery was conducted in GK rats...

Congenital hyperinsulinism (CHI; OMIM: 256450) is characterized by persistent insulin secretion despite severe hypoglycemia. The most common causes are variants in the ATP-binding cassette subfamily C member 8(ABCC8) and potassium inwardly-rectifying channel subfamily J member 11(KCNJ11) genes. These encode ATP-sensitive potassium (KATP ) channel subunit sulfonylurea receptor 1 (SUR1) and inwardly rectifying potassium channel (Kir6.2) proteins. A 7-day-old male infant presented with frequent hypoglycemic episodes and was clinically diagnosed with CHI, underwent trio-whole-exome sequencing, revealing compound heterozygous ABCC8 variants (c...

PURPOSE: LncRNA HCP5 has been reported to participate in high glucose-induced pathological processes, whereas its role in gestational diabetes mellitus (GDM) is unclear. This study aimed to explore the role of HCP5 in GDM. METHODS: This study enrolled a total of 220 pregnant women (gestational age = 1 month). A follow-up study was performed until delivery. The occurrence of GDM was checked every month during follow-up. Plasma samples were collected from all participants and expression of HCP5 was determined with RT-qPCR...

PURPOSE: Prolonged exposure to plasma free fatty acids (FFAs) leads to impaired glucose tolerance (IGT) which can progress to type 2 diabetes (T2D) in the absence of timely and effective interventions. High-fat diet (HFD) leads to chronic inflammation and oxidative stress, impairing pancreatic beta cell (PBC) function. While Didymin, a flavonoid glycoside derived from citrus fruits, has beneficial effects on inflammation dysfunction, its specific role in HFD-induced IGT remains yet to be elucidated...

Elevated concentration of saturated fatty acids in plasma adversely affects pancreatic β-cells, but the effects of unsaturated fatty acids are controversial. In this study, we examined the effects of oleic acid (OA), a monounsaturated fatty acid, on mitochondrial function, which is important for insulin secretion, using INS-1 cells, a pancreatic β-cell line derived from rats. Observations of mitochondrial membrane potential and intracellular ATP concentration showed that the electron transport chain was enhanced and ATP production increased in cells treated with OA, indicating that the response that occurs from sensing an increase in glucose concentration to the production of ATP was accelerated...

Diabetes mellitus (DM) is a metabolic disease characterized by high blood sugar. Due to its complex pathogenesis, no effective drugs have been found so far. Ophiopogonin D (OP-D) has anti-inflammatory, antioxidant, and anticancer activities, but its role in DM has not been studied so far. Hydrogen peroxide (H2 O2 ) was used to induce INS-1 cells. INS-1 cells induced by H2 O2 were treated with OP-D, and cell apoptosis, oxidative stress damage, and related indexes of mitochondrial function were respectively detected by cell counting kit-8, flow cytometry, western blot, enzyme-linked immunosorbent assay, real-time quantitative polymerase chain reaction, JC-1 fluorescent probe, and related kits...

Introduction: Mobilization of intracellular insulin granules to the plasma membrane plays a crucial role in regulating insulin secretion. However, the regulatory mechanisms of this mobilization process have been poorly understood due to technical limitations. In this study, we propose a convenient approach for assessing intracellular insulin granule behavior based on single-molecule analysis of insulin granule membrane proteins labeled with Quantum dot fluorescent nanocrystals. Methods: This approach allows us to analyze intracellular insulin granule movement with subpixel accuracy at 33 fps...

AIMS: Takotsubo syndrome (TTS) is an acute heart failure (AHF) syndrome mimicking the symptoms of acute myocardial infarction. Impaired outcome has been shown, making risk stratification and novel therapeutic concepts a necessity. We hypothesized insulin resistance with elevated plasma glucose and potentially myocardial glucose deprivation to contribute to the pathogenesis of TTS and investigated the therapeutic benefit of insulin in vivo. METHODS AND RESULTS: First, we retrospectively analysed patient data of n = 265 TTS cases (85...

Histone deacetylase inhibitors (HDIs) modulate β cell function in preclinical models of diabetes; however, the mechanisms underlying these beneficial effects have not been determined. In this study, we investigated the impact of the HDI sodium butyrate (NaB) on β cell function and calcium (Ca 2+ ) signaling using ex vivo and in vitro models of diabetes. Our results show that NaB significantly improved glucose-stimulated insulin secretion in islets from human organ donors with type 2 diabetes and in cytokine-treated INS-1 β cells...

Cocaine and amphetamine-regulated transcript (CART) is expressed in pancreatic islet cells and neuronal elements. We have previously established insulinotropic actions of CART in human and rodent islets. The receptor for CART in the pancreatic beta cells is unidentified. We used RNA sequencing of Cartpt knockdown (KD) INS-1 832/13 cells and identified GPR162 as the most Cartpt -regulated receptor. We therefore tested if GPR162 mediates the effects of CART in beta cells. Binding of CART to GPR162 was established using proximity ligation assay, radioactive binding, and co-immunoprecipitation, and KD of Gpr162 mRNA caused reduced binding...

Emerging evidence implicates novel roles for small G protein GDP dissociation stimulator (smgGDS) in G protein activation and subsequent targeting to relevant subcellular compartments for effector regulation. Given the well-established roles of small G proteins in insulin secretion, we undertook this investigation to determine the putative roles of smgGDS in insulin secretion. Immunoblotting studies revealed that both splice variants of smgGDS are expressed in human islets, rat islets and INS-1 832/13 cells...

Di-(2-ethylhexyl)-phthalate (DEHP), a common Phthalic acid ester (PAEs), has been reported to be associated with diabetes mellitus, yet the underlying mechanisms remain unknown. Combined nutrient interventions have been shown to alleviate the diabetic toxicity of DEHP. However, the effects and mechanisms of the combined intervention of Astragalus and vitamins (C and E) are currently unknown. In this study, we investigated the potential mechanisms of DEHP-induced diabetes mellitus through transcriptome analysis and vitro experiments using rat insulinoma cells (INS-1 cells)...

Pancreatic beta cells secrete insulin in response to plasma glucose. The ATP-sensitive potassium channel (KATP ) links glucose metabolism to islet electrical activity in these cells by responding to increased cytosolic [ATP]/[ADP]. It was recently proposed that pyruvate kinase (PK) in close proximity to beta cell KATP locally produces the ATP that inhibits KATP activity. This proposal was largely based on the observation that applying phosphoenolpyruvate (PEP) and ADP to the cytoplasmic side of excised inside-out patches inhibited KATP ...

Glucagon-like peptide-1 (GLP-1) has gained much attention in the last decade for the treatment of type 2 diabetes. Accumulating evidence indicates that some metabolites of GLP-1 have biological activities that might contribute to the pleiotropic effects of GLP-1 independent of the GLP-1 receptor. The hypoglycemic and weight-reducing effects of the reported metabolites and modifications still need to be confirmed. In this study, we started from the C-terminal nonapeptide GLP-1(28-36) amide and developed a series of GLP-1(28-36) amide-derived hybrid peptides...