Nondiabetic Pancreas Research Articles

Human Pancreatic Islet Gene View in glucose homeostasis of Diabetic and Non-Diabetic Pancreases in the Indian population

Human Pancreatic Islet Gene View in glucose homeostasis of Diabetic and Non-Diabetic Pancreases in the Indian population

Characteristics of research-focused human islet preparations from organ donors with type 2 diabetes

ABSTRACT Type 2 diabetes mellitus (T2D) affects 463 million individuals worldwide. β-cell dysfunction and relatively inadequate β-cell mass has been implicated in the pathogenesis of T2D. Primary human islets from T2D patients can reveal the islet dysfunction and the underlying mechanisms and thus have become valued resources for diabetes research. Our center (Human Islet Resource Center, China) has prepared a number of batches of human islets from T2D organ donors. The present study aims to characterize islet isolation processes, islet yields, and qualities of T2D pancreases by comparing with non-diabetic (ND) ones. Overall, 24 T2D and 80 ND pancreases were obtained with informed research consents. The digestion time, islet purity, yield, size distribution, islet morphology score, viability, and function in each islet preparation were analyzed. We found that at digestion stage, T2D pancreases need significantly longer digestion duration and have worse digestion rates and lower gross islet yields. At purification stage, T2D pancreases have poorer purity, purification rate, morphology score, and islet yields after purification. Functional evaluation by GSI assay showed that the human T2D islets have significantly lower glucose stimulated insulin secretion ability. In conclusion, the features of longer digestion duration, lower yields and quality, and impaired insulin secretion in T2D group are consistent with the pathological condition of this disease. Both islet yields and islet function evaluation results did not support human T2D islets as clinical transplantation resources. However, they could serve as good research models for T2D disease studies and promote the advancement of diabetes research.

U-shaped association between serum IGF2BP3 and T2DM: A cross-sectional study in Chinese population.

To clarify the expression of N6-methyladenosine (m6 A) modulators involved in the pathogenesis of type 2 diabetes mellitus (T2DM). We further explored the association of serum insulin-like growth factor 2 mRNA-binding proteins 3 (IGF2BP3) levels and odds of T2DM in a high-risk population. The gene expression data set GSE25724 was obtained from the Gene Expression Omnibus, and a cluster heatmap was generated by using the R package ComplexHeatmap. Differential expression analysis for 13 m6 A RNA methylation regulators between nondiabetic controls and T2DM subjects was performed using an unpaired t test. A cross-sectional design, including 393 subjects (131 patients with newly diagnosed T2DM, 131 age- and sex-matched subjects with prediabetes, and 131 healthy controls), was carried out. The associations between serum IGF2BP3 concentrations and T2DM were modeled by restricted cubic spline and logistic regression models. Two upregulated (IGF2BP2 and IGF2BP3) and 5 downregulated (methyltransferase-like 3 [METTL3], alkylation repair homolog protein 1 [ALKBH1], YTH domain family 2 [YTHDF2], YTHDF3, and heterogeneous nuclear ribonucleoprotein [HNRNPC]) m6 A-related genes were found in islet samples of T2DM patients. A U-shaped association existed between serum IGF2BP3 levels and odds of T2DM according to cubic natural spline analysis models, after adjustment for body mass index, waist circumference, diastolic blood pressure, total cholesterol, and triglyeride. Multivariate logistic regression showed that progressively higher odds of T2DM were observed when serum IGF2BP3 levels were below 0.62 ng/mL (odds ratio 3.03 [95% confidence interval 1.23-7.47]) in model 4. Seven significantly altered m6 A RNA methylation genes were identified in T2DM. There was a U-shaped association between serum IGF2BP3 levels and odds of T2DM in the general Chinese adult population. This study provides important evidence for further examination of the role of m6 A RNA methylation, especially serum IGF2BP3 in T2DM risk assessment.

Redefining the tail of pancreas based on the islets microarchitecture and inter-islet distance: An immunohistochemical study.

Researchers divided the pancreas distal to the neck into 2 equal parts as the body and tail region by an arbitrary line. Surgeons considered the part of the pancreas, left to the aorta as the tail region. We performed this study to identify the transition zone of low-density to high-density islet cells for redefining the tail region.We quantified islets area proportion, beta-cell area proportion, and inter-islet distance in 9 Indian-adult-human non-diabetic pancreases from autopsy by using anti-synaptophysin and anti-insulin antibodies. Data were categorized under 3 regions like the proximal body, distal body, and distal part of the pancreas.Islet and beta-cell area proportion are progressively increased from head to tail region of the pancreas with a significant reduction in inter-islet distance and beta-cell percentage distal to the aorta. There is no significant difference in inter-islet distance and beta-cell percentage of the distal part of the body and tail region.Crowding of islets with intermingled microarchitecture begins in the pancreas distal to the aorta, which may be the beginning of the actual tail region. This study will provide insight into the preservation of islets-rich part of the pancreas during pancreatectomy and future prediction of new-onset diabetes.

Association of Type 2 Diabetes with Submicron Titanium Dioxide Crystals in the Pancreas.

Pigment-grade titanium dioxide (TiO2) of 200-300 nm particle diameter is the most widely used submicron-sized particle material. Inhaled and ingested TiO2 particles enter the bloodstream, are phagocytized by macrophages and neutrophils, are inflammatory, and activate the NLRP3 inflammasome. In this pilot study of 11 pancreatic specimens, 8 of the type 2 diabetic pancreas and 3 of the nondiabetic pancreas, we show that particles comprising 110 ± 70 nm average diameter TiO2 monocrystals abound in the type 2 diabetic pancreas, but not in the nondiabetic pancreas. In the type 2 diabetic pancreas, the count of the crystals is as high as 108-109 per gram.

A search for candidate viruses in type 1 diabetic pancreas using the polymerase chain reaction.

In order to investigate a possible viral aetiology for Type 1 diabetes the polymerase chain reaction (PCR) technique was used. Pancreatic tissue from Type 1 diabetic subjects was examined for the presence of a panel of common viruses. Primers specific for mumps, measles, cytomegalovirus, and Epstein Barr virus, as well as primers located in a highly conserved region of the enterovirus genome which are capable of detecting all of the following family members: Coxsackie B, echovirus, polio, mengovirus, and encephalomyocarditis virus were used to screen 18 Type 1 diabetic subjects of whom 3 had proven insulitis, 12 Type 2 diabetic subjects and 18 non-diabetic controls. Epstein Barr virus was detected in two Type 1 (13%), two Type 2 (22%), and three of the normal nondiabetic pancreases (20%), and the DNA sequences confirmed by direct sequencing. Cytomegalovirus was detected in one of the normal pancreases only and no evidence of any of the other viruses was found. It is concluded that the Type 1 diabetic pancreatic samples studied did not show persistence of infection with any of the above viruses. Non-persistent acute infection of the pancreas by the above viruses cannot be excluded in the aetiology of Type 1 diabetes from this study.

Pancreastatin concentration in diabetic and non-diabetic pancreas

Pancreastatin concentration in diabetic and non-diabetic pancreas

Autonomic innervation of the pancreas in diabetic and non-diabetic rats. A new view on intramural sympathetic structural organization

Using histochemical and immunocytochemical methods the intramural neural tissue of the pancreas was investigated in non-diabetic and in alloxan-diabetic rats. It was demonstrated that the non-diabetic pancreas contains an average of 2.71 cells/mm 3 tissue that react positive for activity of acetylcholinesterase and 2.38 cells/mm 3 tissue that show monoamine oxidase activity. Both cholinergic and monoaminergic cells are found as solitary cells and in clusters of various sizes. All these cells are embedded in the exocrine tissue. Both histochemical methods revealed the presence of intra-insular fiber plexuses. Treatment with alloxan resulted in disappearence of intra-insular cholinergic and monoaminergic activity and also in a 68% reduction of the cholinergic cells and 54% of the monoaminergic cells in the diabetic pancreas. Application of immunocytochemical methods employing antibodies against norepinephrine and dopamine demonstrated the noradrenergic character of at least some of the monoaminergic cell groups. It is discussed how the present data and data from previous innervation studies provide evidence for an intramural ganglionic organization of the sympathetic innervation of the rat pancreas.

Regulatory effects of insulin and experimental diabetes on neutral amino acid transport in the perfused rat exocrine pancreas. Kinetics of unidirectional l-serine influx and efflux at the basolateral plasma membrane

Relatively little is known about the hormonal regulation of amino acid transport in the normal and diabetic exocrine pancreas. In this study unidirectional influx and tracer efflux of l-serine at the basolateral interface of the rat pancreatic epithelium was investigated in the perfused exocrine pancreas using a rapid (< 30 s) paired-tracer dilution technique. In the non-diabetic pancreas l-serine influx was saturable and stimulated by perfusion with exogenous bovine insulin (100 μU/ml). Transport of l-serine and methylaminoisobutyric acid was markedly elevated in pancreata isolated from streptozotocin diabetic rats and insulin partially reversed the stimulation of l-serine transport induced by experimental diabetes. These results suggest that insulin and diabetes modulate the epithelial transport activity for small neutral amino acids in the intact exocrine pancreas.

Pancreatic polypeptide and insulin contents in diabetic and nondiabetic human pancreas and their relationship to the stability of the fasting serum glucose.

The amounts of insulin and pancreatic polypeptide (PP) in twenty four autopsied diabetic and nineteen nondiabetic human pancreases were determined and their relationship to the stability of the fasting serum glucose level was investigated. The PP content of the tail of the pancreas in diabetic and nondiabetic subjects was 9.55 +/- 2.41 and 7.71 +/- 1.52 micrograms/g pancreas, and that of the head of the pancreas was 16.86 +/- 5.51 and 15.82 +/- 5.38 micrograms/g, respectively. No significant differences in content were found between diabetic and nondiabetic pancreases. The PP content of the head pancreas of some diabetics and nondiabetics was higher than that of the tail. The insulin content of the tail of the diabetic pancreas was lower than that of the nondiabetic pancreas. In those diabetics where there was less than 0.5 U/g of insulin in the tail pancreas, the stability of the fasting serum glucose was very poor, indicating an unstable type of diabetes. There was a significant inverse correlation between standard deviation of FBS and the amount of insulin, but the PP content of the pancreas had no relation to the stability of the fasting serum glucose.

Studies of human insulin from nondiabetic and diabetic pancreas.

Insulin has been isolated from single human pancreases from diabetic and nondiabetic sources. Purification was accomplished primarily by gel filtration. The average yield of insulin from the nondiabetic pancreas was 8.6 mg. per 100 gm. of tissue, and from the diabetic pancreas 2.9 mg. per 100 gm. The amino acid composition of nondiabetic insulin was in agreement with the known structure of human insulin. The insulin isolated from the diabetic pancreas had the same amino acid composition as normal human insulin in all cases but one. Based upon the amino acid analysis, it is possible that a different amino acid sequence occurs in the insulin from this diabetic source.