I2018

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Decreased Expression of Cilia Genes in Pancreatic Islets as a Risk Factor for Type 2 Diabetes in Mice and Humans.

Oliver Kluth et al.

Cell reports, 26(11), 3027-3036 (2019-03-14)

An insufficient adaptive beta-cell compensation is a hallmark of type 2 diabetes (T2D). Primary cilia function as versatile sensory antennae regulating various cellular processes, but their role on compensatory beta-cell replication has not been examined. Here, we identify a significant

The P2X7 receptor and pannexin-1 are involved in glucose-induced autocrine regulation in β-cells.

Marco Tozzi et al.

Scientific reports, 8(1), 8926-8926 (2018-06-14)

Extracellular ATP is an important short-range signaling molecule that promotes various physiological responses virtually in all cell types, including pancreatic β-cells. It is well documented that pancreatic β-cells release ATP through exocytosis of insulin granules upon glucose stimulation. We hypothesized

Superiority of small islets in human islet transplantation.

Roger Lehmann et al.

Diabetes, 56(3), 594-603 (2007-03-01)

Many factors influence the outcome of islet transplantation. As islets in the early posttransplant setting are supplied with oxygen by diffusion only and are in a hypoxic state in the portal system, we tested whether small human islets are superior

Islet Interleukin-1β Immunoreactivity Is an Early Feature of Cystic Fibrosis That May Contribute to β-Cell Failure.

Rebecca L Hull et al.

Diabetes care, 41(4), 823-830 (2018-02-14)

Cystic fibrosis-related diabetes (CFRD) is a common complication of cystic fibrosis (CF), increasing patient morbidity and mortality. Poor understanding of CFRD pathogenesis limits the development of targeted therapies to treat and/or prevent the disease. The aim of this study was

Targeted deletion of Insm2 in mice result in reduced insulin secretion and glucose intolerance.

Lin Wang et al.

Journal of translational medicine, 16(1), 297-297 (2018-10-26)

Neurogenin3 (Ngn3) and neurogenic differentiation 1 (NeuroD1), two crucial transcriptional factors involved in human diabetes (OMIM: 601724) and islet development, have been previously found to directly target to the E-boxes of the insulinoma-associated 2 (Insm2) gene promoter, thereby activating the

Dietary Protein to Carbohydrate Ratio and Caloric Restriction: Comparing Metabolic Outcomes in Mice.

Samantha M Solon-Biet et al.

Cell reports, 11(10), 1529-1534 (2015-06-02)

Both caloric restriction (CR) and low-protein, high-carbohydrate (LPHC) ad-libitum-fed diets increase lifespan and improve metabolic parameters such as insulin, glucose, and blood lipids. Severe CR, however, is unsustainable for most people; therefore, it is important to determine whether manipulating macronutrient

Effect of a neural relay on liver regeneration in mice: activation of serotonin release from the gastrointestinal tract.

Ryosuke Inoue et al.

FEBS open bio, 8(3), 449-460 (2018-03-08)

The development of therapeutic options to promote hepatic regeneration following severe liver injury is essential. While humoral factors have been reported as mechanisms of liver regeneration, the contributions of interorgan communication to liver regeneration have not been reported. In this

In vivo hyperglycaemia exposure elicits distinct period-dependent effects on human pancreatic progenitor differentiation, conveyed by oxidative stress.

Thomas A Legøy et al.

Acta physiologica (Oxford, England), 228(4), e13433-e13433 (2019-12-25)

The loss of insulin-secreting β-cells, ultimately characterizing most diabetes forms, demands the development of cell replacement therapies. The common endpoint for all ex vivo strategies is transplantation into diabetic patients. However, the effects of hyperglycaemia environment on the transplanted cells

Long-Term Expansion of Pancreatic Islet Organoids from Resident Procr+ Progenitors.

Daisong Wang et al.

Cell, 180(6), 1198-1211 (2020-03-24)

It has generally proven challenging to produce functional β cells in vitro. Here, we describe a previously unidentified protein C receptor positive (Procr+) cell population in adult mouse pancreas through single-cell RNA sequencing (scRNA-seq). The cells reside in islets, do not

A surrogate of Roux-en-Y gastric bypass (the enterogastro anastomosis surgery) regulates multiple beta-cell pathways during resolution of diabetes in ob/ob mice.

Chloé Amouyal et al.

EBioMedicine, 58, 102895-102895 (2020-08-03)

Bariatric surgery is an effective treatment for type 2 diabetes. Early post-surgical enhancement of insulin secretion is key for diabetes remission. The full complement of mechanisms responsible for improved pancreatic beta cell functionality after bariatric surgery is still unclear. Our

GDH-Dependent Glutamate Oxidation in the Brain Dictates Peripheral Energy Substrate Distribution.

Melis Karaca et al.

Cell reports, 13(2), 365-375 (2015-10-07)

Glucose, the main energy substrate used in the CNS, is continuously supplied by the periphery. Glutamate, the major excitatory neurotransmitter, is foreseen as a complementary energy contributor in the brain. In particular, astrocytes actively take up glutamate and may use

Deconstructing the origins of sexual dimorphism in sensory modulation of pancreatic β cells.

Sara McEwan et al.

Molecular metabolism, 53, 101260-101260 (2021-05-24)

The regulation of glucose-stimulated insulin secretion and glucose excursion has a sensory component that operates in a sex-dependent manner. Here, we aim to dissect the basis of the sexually dimorphic interaction between sensory neurons and pancreatic β cells and its

Insulin therapy for pre-hyperglycemic beta-cell endoplasmic reticulum crowding.

Afaf Absood et al.

PloS one, 8(2), e54351-e54351 (2013-02-15)

Insulin therapy improves β-cell function in early stages of diabetes by mechanisms that may exceed alleviation of glucotoxicity. In advance type 2 diabetes, hyperglycemia causes β-cell damage and ultimately β-cell loss. At such an advanced stage, therapeutic modalities are often

The Effect of Wnt Pathway Modulators on Human iPSC-Derived Pancreatic Beta Cell Maturation.

Heidrun Vethe et al.

Frontiers in endocrinology, 10, 293-293 (2019-05-30)

Current published protocols for targeted differentiation of human stem cells toward pancreatic β-cells fail to deliver sufficiently mature cells with functional properties comparable to human islet β-cells. We aimed to assess whether Wnt-modulation could promote the final protocol stages of

Loss of GATA4 causes ectopic pancreas in the stomach.

Elisa Rodríguez-Seguel et al.

The Journal of pathology, 250(4), 362-373 (2019-12-27)

Pancreatic heterotopia is defined as pancreatic tissue outside its normal location in the body and anatomically separated from the pancreas. In this work we have analyzed the stomach glandular epithelium of Gata4 flox/flox ; Pdx1-Cre mice (Gata4KO mice). We found

FAM3A plays crucial roles in controlling PDX1 and insulin expressions in pancreatic beta cells.

Weili Yang et al.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 34(3), 3915-3931 (2020-01-17)

So far, the mechanism that links mitochondrial dysfunction to PDX1 inhibition in the pathogenesis of pancreatic β cell dysfunction under diabetic condition remains largely unclear. This study determined the role of mitochondrial protein FAM3A in regulating PDX1 expression in pancreatic

Use of the PET ligand florbetapir for in vivo imaging of pancreatic islet amyloid deposits in hIAPP transgenic mice.

Andrew T Templin et al.

Diabetologia, 61(10), 2215-2224 (2018-07-27)

Islet amyloid deposits contribute to beta cell dysfunction and death in most individuals with type 2 diabetes but non-invasive methods to determine the presence of these pathological protein aggregates are currently not available. Therefore, we examined whether florbetapir, a radiopharmaceutical

Olfactory receptors are expressed in pancreatic β-cells and promote glucose-stimulated insulin secretion.

Yuichiro Munakata et al.

Scientific reports, 8(1), 1499-1499 (2018-01-26)

Olfactory receptors (ORs) mediate olfactory chemo-sensation in OR neurons. Herein, we have demonstrated that the OR chemo-sensing machinery functions in pancreatic β-cells and modulates insulin secretion. First, we found several OR isoforms, including OLFR15 and OLFR821, to be expressed in

Sequential in vivo labeling of insulin secretory granule pools in INS-SNAP transgenic pigs.

Elisabeth Kemter et al.

Proceedings of the National Academy of Sciences of the United States of America, 118(37) (2021-09-12)

β cells produce, store, and secrete insulin upon elevated blood glucose levels. Insulin secretion is a highly regulated process. The probability for insulin secretory granules to undergo fusion with the plasma membrane or being degraded is correlated with their age.

Therapeutic effect of melatonin-loaded chitosan/lecithin nanoparticles on hyperglycemia and pancreatic beta cells regeneration in streptozotocin-induced diabetic rats.

Habiba Alaa et al.

Scientific reports, 13(1), 10617-10617 (2023-07-01)

Nanotechnology is used to overcome fundamental flaws in today's marketed pharmaceuticals that obstruct therapy, like restricted solubility and quick release of drugs into the bloodstream. In both human and animal researches, melatonin was demonstrated to regulate glucose levels. Despite the

Reprogrammed keratinocytes from elderly type 2 diabetes patients suppress senescence genes to acquire induced pluripotency.

Seiga Ohmine et al.

Aging, 4(1), 60-73 (2012-02-07)

Nuclear reprogramming enables patient-specific derivation of induced pluripotent stem (iPS) cells from adult tissue. Yet, iPS generation from patients with type 2 diabetes (T2D) has not been demonstrated. Here, we report reproducible iPS derivation of epidermal keratinocytes (HK) from elderly

The combined effect of mesenchymal stem cells and resveratrol on type 1 diabetic neuropathy.

Chen Wang et al.

Experimental and therapeutic medicine, 17(5), 3555-3563 (2019-04-17)

Diabetic neuropathy (DN) is one of the most common diabetic complications that results in an increase in patient discomfort and pain. The present study demonstrated that mesenchymal stem cells (MSCs) or resveratrol (RSV) may improve diabetic hyperglycemia and neuropathy. The

17β-Estradiol Promotes Islet Cell Proliferation in a Partial Pancreatectomy Mouse Model.

Tingting Wu et al.

Journal of the Endocrine Society, 1(7), 965-979 (2017-12-22)

17β-Estradiol (E2) is a multifunctional steroid hormone in modulating metabolism in vivo. Previous studies have reported that E2 could promote insulin secretion and protect β cells from apoptosis. In this study, the partial pancreatectomy (PPx) model was used to study

Defective liver glycogen autophagy related to hyperinsulinemia in intrauterine growth-restricted newborn wistar rats.

Juan de Toro-Martín et al.

Scientific reports, 10(1), 17651-17651 (2020-10-21)

Maternal malnutrition plays a critical role in the developmental programming of later metabolic diseases susceptibility in the offspring, such as obesity and type 2 diabetes. Because the liver is the major organ that produces and supplies blood glucose, we aimed

Taurine Ameliorates Streptozotocin-Induced Diabetes by Modulating Hepatic Glucose Metabolism and Oxidative Stress in Mice.

Shigeru Murakami et al.

Metabolites, 12(6) (2022-06-24)

Taurine is a sulfated amino acid derivative that plays an important role in maintaining the cell function of the living body. Although taurine has been shown to ameliorate diabetes, its mechanism of action has not yet been fully elucidated. The

Amelioration of streptozotocin-induced diabetes in mice with cells derived from human marrow stromal cells.

Min Zhao et al.

PloS one, 3(7), e2666-e2666 (2008-07-17)

Pluri-potent bone marrow stromal cells (MSCs) provide an attractive opportunity to generate unlimited glucose-responsive insulin-producing cells for the treatment of diabetes. We explored the potential for human MSCs (hMSCs) to be differentiated into glucose-responsive cells through a non-viral genetic reprogramming

Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels.

Gozde Uzunalli et al.

Acta biomaterialia, 22, 8-18 (2015-05-02)

Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a

Rheb1 promotes glucose-stimulated insulin secretion in human and mouse β-cells by upregulating GLUT expression.

Yan Yang et al.

Metabolism: clinical and experimental, 123, 154863-154863 (2021-08-11)

Reduced β-cell mass and impaired β-cell function are primary causes of all types of diabetes. However, the intrinsic molecular mechanism that regulates β-cell growth and function remains elusive. Here, we demonstrate that the small GTPase Rheb1 is a critical regulator

Metabolic endotoxemia initiates obesity and insulin resistance.

Cani P D, et al.

Diabetes, 56(7), 1761-1772 (2007)

Interactions between important regulatory proteins and human alphaB crystallin.

Joy G Ghosh et al.

Biochemistry, 46(21), 6308-6317 (2007-05-10)

Protein pin arrays assessed interactions between alphaB crystallin and 12 regulatory proteins, including EGF, FGF-2, IGF-1, NGF-beta, TGF-beta, VEGF, insulin, beta-catenin, caspase-3, caspase-8, Bcl-2, and Bcl-xL, which are important in cellular differentiation, proliferation, signaling, cytoskeletal assembly, and apoptosis. FGF-2, NGF-beta

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