Pancreatic islets

OBJECTIVES: Total pancreatectomy and islet autotransplantation (TPIAT) for pancreatitis may induce risk for essential fatty acid deficiency (EFAD) due to exocrine pancreatic insufficiency and intestinal alterations. The prevalence of EFAD post-TPIAT is currently unknown. METHODS: We abstracted essential fatty acid (EFA) profiles (n = 332 samples) for 197 TPIAT recipients (72% adult, 33% male). Statistical analyses determined the prevalence of, and associations with, EFAD post-operatively...

OBJECTIVES: Total pancreatectomy with islet autotransplantation (TPIAT) is performed to improve the quality of life (QOL) of patients with chronic pancreatitis. Few reports have documented QOL following TPIAT, with none using the pancreatitis-specific Pancreatitis Quality of Life Instrument (PANQOLI). We surveyed patients at our center who underwent TPIAT to document postoperative QOL. METHODS: We collected survey data from 18 adult patients who underwent TPIAT at our medical center from 2012 to 2020...

In diabetes, macrophages and inflammation are increased in the islets, along with β-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in β-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS...

Pancreatic endocrine cells employ a sophisticated system of paracrine and autocrine signals to synchronize their activities, including glutamate which controls hormone release and β-cell viability by acting on glutamate receptors expressed by endocrine cells. We here investigate whether alteration of the Excitatory Amino Acid Transporter 2 (EAAT2), the major glutamate clearance system in the islet, may occur in type 2 diabetes mellitus (T2DM) and contribute to β-cell dysfunction. Increased EAAT2 intracellular localization was evident in islets of Langerhans from T2DM subjects as compared with healthy control subjects, despite similar expression levels...

BACKGROUND: Current approaches to profile the single-cell transcriptomics of human pancreatic endocrine cells almost exclusively rely on freshly isolated islets. However, human islets are limited in availability. Furthermore, the extensive processing steps during islet isolation and subsequent single cell dissolution might alter gene expressions. In this work, we report the development of a single-nucleus RNA sequencing (snRNA-seq) approach with targeted islet cell enrichment for endocrine-population focused transcriptomic profiling using frozen archival pancreatic tissues without islet isolation...

Autoreactive CD8+ T cells play a key role in type 1 diabetes (T1D), but the antigen spectrum that activates autoreactive CD8+ T cells remains unclear. Endoplasmic reticulum stress (ERS) has been implicated in β-cell autoantigen generation. Here, we analyzed the major histocompatibility complex class I (MHC-I)-associated immunopeptidome (MIP) of islet β-cells under steady and ERS conditions and found that ERS reshaped the MIP of β-cells and promoted the MHC-I presentation of a panel of conventional self-peptides...

Diabetes mellitus (DM) is an uncommon, poorly documented metabolic disorder of birds. Extrapolating knowledge from DM in mammals is challenging because of marked differences in avian physiology and metabolism. A literature review from December 1991 to January 2022 identified 14 publications covering 16 diabetic birds, 63% (10/16) of which belonged to the order Psittaciformes with Ara as the predominant genus. No sex predilection was noted, but males generally presented at a younger age. Commonly reported clinical signs included polyuria 94% (15/16), polydipsia 88% (14/16), weight loss 75% (12/16), lethargy 63% (10/16), and polyphagia 38% (6/16)...

Type 1 diabetes (T1D) is a chronic condition in which beta cells are destroyed by immune cells. Despite progress in immunotherapies that could delay T1D onset, early detection of autoimmunity remains challenging. Here, we evaluate the utility of machine learning for early prediction of T1D using single-cell analysis of islets. Using gradient-boosting algorithms, we model changes in gene expression of single cells from pancreatic tissues in T1D and non-diabetic organ donors. We assess if mathematical modeling could predict the likelihood of T1D development in non-diabetic autoantibody-positive donors...

Recent studies have shown that maternal vitamin D deficiency (VDD) causes long-term metabolic changes in offspring. However, little is known about the impact of maternal VDD on offspring endocrine pancreas development and insulin secretion in the adult life of male and female animals. Female rats (Wistar Hannover) were fed either control (1000 IU Vitamin D3/kg), VDD (0 IU Vitamin D3/kg), or a Ca2+ -enriched VDD diet (0 IU Vitamin D3/kg + Ca2+ and P/kg) for 6 weeks and during gestation and lactation. At weaning, VDD status was confirmed based on low serum calcidiol levels in dams and pups...

Perfluorooctanesulfonic acid (PFOS) is a ubiquitous legacy environmental contaminant detected broadly in human samples and water supplies. PFOS can cross the placenta and has been detected in cord blood and breastmilk samples, underscoring the importance of understanding the impacts of maternal PFOS exposure during early development. This study aimed to investigate the effects of a preconception exposure to PFOS on developmental endpoints in offspring, as well as examine the role of the transcription factor Nuclear factor erythroid-2-related factor (Nrf2a) in mediating these effects...

We aimed to determine if cheese could reduce glucose intolerance in aged rats with overt type 2 diabetes (T2D). Male Sprague-Dawley rats treated with high-fat diet and streptozotocin (STZ) exhibited hyperglycemia to elicit T2D. One week after STZ injection, low-fat (LOW) or regular-fat (REG) cheese was provided for 5 weeks and compared with T2D and low-fat diet reference (REF) groups. Food intake and weight gain were similar in all groups. Oral glucose tolerance tests revealed glucose intolerance in T2D rats that was partially ameliorated by LOW but not REG...

Interleukin-6 (IL6) is a pleiotropic cytokine implicated in metabolic disorders and inflammation, yet its precise influence on insulin secretion and glucose metabolism remains uncertain. This study examined IL6 expression in pancreatic islets from individuals with/without diabetes, alongside a series of functional experiments, including siRNA silencing; IL6 treatment; and assessments of glucose uptake, cell viability, apoptosis, and expression of key β-cell genes, which were conducted in both INS-1 cells and human islets to elucidate the effect of IL6 on insulin secretion...

OBJECTIVE: Maturity-onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY...

Amylin is a systemic neuroendocrine hormone co-expressed and co-secreted with insulin by pancreatic β-cells. In persons with thype-2 diabetes, amylin forms pancreatic amyloid triggering inflammasome and interleukin-1β signaling and inducing β-cell apoptosis. Here, we summarize recent progress in understanding the potential link between amyloid-forming pancreatic amylin and Alzheimer's disease (AD). Clinical data describing amylin pathology in AD alongside mechanistic studies in animals are reviewed...

Glucose homeostasis is mainly under the control of the pancreatic islet hormones insulin and glucagon, which, respectively, stimulate glucose uptake and utilization by liver, fat, and muscle or glucose production by the liver. The balance between the secretion of these hormones is under the control of blood glucose concentrations. Indeed, pancreatic islet b-cells and a-cells can sense variations in glycemia and respond by an appropriate secretory response to restore euglycemia. However, the secretory activity of these cells is also under multiple additional metabolic, hormonal, and neuronal signals that combine to ensure the perfect control of glycemia over a lifetime...

Proposed mechanisms by which disruption of endogenous dsRNA editing in β-cells leads to type 1 diabetes-like phenotypes in βAdarKO mice. Disruption of endogenous dsRNA editing in β-cells initiates IFN responses, thereby inducing pancreatic islet inflammation and β-cell dysfunction. Hyperglycemia induced by β-cell dysfunction further promotes islet inflammation, likely via increased dsRNA resulting from increased β-cell workload, thereby producing a vicious cycle. The mechanism by which impairment of dsRNA editing is integrated with autoimmune-mediated pathogenesis of type 1 diabetes remains to be clarified...

Variants at the SLC30A8 locus are associated with type 2 diabetes (T2D) risk. The lead variant, rs13266634, encodes an amino acid change, Arg325Trp (R325W), at the C-terminus of the secretory granule-enriched zinc transporter, ZnT8. Although this protein-coding variant was previously thought to be the sole driver of T2D risk at this locus, recent studies have provided evidence for lowered expression of SLC30A8 mRNA in protective allele carriers. In the present study, we examined multiple variants that influence SLC30A8 allele-specific expression...

Stress-induced islet graft loss during the peri-transplantation period reduces the efficacy of islet transplantation. In this prospective, randomized, double-blind clinical trial, we evaluated the safety and efficacy of 60 mg/kg human alpha-1 antitrypsin (AAT) or placebo infusion weekly for four doses beginning before surgery in chronic pancreatitis (CP) patients undergoing total pancreatectomy and islet autotransplantation (TP-IAT). Subjects were followed for 12 months post-TP-IAT. The dose of AAT was safe, as there was no difference in the types and severity of adverse events in participants from both groups...

PURPOSE: To evaluate the effect and mechanism of 1,25(OH)2 D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). METHODS: A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2 D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining...

The angiotensin-converting enzyme 2 (ACE2) is a primary cell surface viral binding receptor for SARS-CoV-2, so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19. In the current study, we utilized islet organoids derived from human embryonic stem cells (hESCs), animal models and COVID-19 patients to discover that fibroblast growth factor 7 (FGF7) enhances ACE2 expression within the islets, facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion...