scholarly journals The Role of Vegan Diets in Lipotoxicity-Induced Beta-Cell Dysfunction in Type-2-Diabetes

2020 ◽  
Vol 27 (SP2) ◽  
pp. e22-e38
Author(s):  
Maximilian Andreas Storz
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Cell Function ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction

Type-2-diabetes is considered the new plague of the current century and both, its incidence and prevalence are rapidly increasing. Chronic insulin resistance and a progressive decline in beta-cell function are discussed as the root causes of type-2-diabetes. Both were associated with obesity and pathologically elevated concentrations of circulating free fatty acids in the blood. The harmful effects of chronically elevated free fatty acid levels on glucose homeostasis and non-adipose tissues are referred to as lipotoxicity. Pancreatic beta-cells appear to be particularly vulnerable and both, dietary fat quantity and quality may impact beta-cell function. Diets high in saturated fats are especially harmful to beta-cells while (poly-)unsaturated fatty acids were associated with beta-cell protective effects. This review examined how a dietary modification towards a low-fat vegan diet, which is particularly low in saturated and trans-fats, could help to prevent or reduce lipotoxicity-induced beta cell dysfunction. Several potential mechanisms of action were identified including: (1) reduced total fat intake (fat quantity), (2) a more favorable polyunsaturated fatty acid to saturated fatty acid ratio (fat quality), (3) improved body weight and a reduction in adipose tissue mass, and finally (4) improved glycemic control. The latter appears of paramount importance in light of the accumulating evidence that lipotoxic events are tightly coupled to excess glucose levels. All four mechanisms are likely to contribute complementarily to improved beta-cell function in individuals with type-2-diabetes and may reduce the likelihood of lipotoxic events to occur. Physicians must consider these findings when counseling patients on lifestyle and nutrition.

scholarly journals JOE DOUPE LECTURE: Emerging Strategies for the Preservation of Pancreatic Beta-cell Function in early Type 2 Diabetes

2014 ◽  
Vol 37 (6) ◽  
pp. 414 ◽  
Author(s):  
Ravi Retnakaran
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Fundamental Problem ◽  
Pancreatic Beta Cell ◽  
Beta Cell Dysfunction ◽  
Cell Dysfunction ◽  
Pancreatic Beta Cell Function

A fundamental problem in the clinical management of type 2 diabetes is the inability to prevent the ongoing deterioration of pancreatic beta-cell function over time that underlies the chronic progressive nature of this condition. Importantly, beta-cell dysfunction has both reversible and irreversible components. Furthermore, the amelioration of reversible beta-cell dysfunction through the early institution of short-term insulin-based therapy has emerged as a strategy that can yield temporary remission of type 2 diabetes. In this context, we have forwarded a novel therapeutic paradigm consisting of initial induction therapy to improve beta-cell function early in the course of diabetes followed by maintenance therapy aimed at preserving this beneficial beta-cell effect. Ultimately, this approach may yield an optimized therapeutic strategy for the durable preservation of beta-cell function and consequent modification of the natural history of type 2 diabetes.

scholarly journals Structure-functional changes in eNAMPT at high concentrations mediate mouse and human beta cell dysfunction in type 2 diabetes

Diabetologia ◽  
2019 ◽  
Vol 63 (2) ◽  
pp. 313-323 ◽  
Author(s):  
Sophie R. Sayers ◽  
Rebecca L. Beavil ◽  
Nicholas H. F. Fine ◽  
Guo C. Huang ◽  
Pratik Choudhary ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Beta Cell Dysfunction ◽  
Functional Changes ◽  
Cell Dysfunction

Abstract Aims/hypothesis Progressive decline in functional beta cell mass is central to the development of type 2 diabetes. Elevated serum levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) are associated with beta cell failure in type 2 diabetes and eNAMPT immuno-neutralisation improves glucose tolerance in mouse models of diabetes. Despite this, the effects of eNAMPT on functional beta cell mass are poorly elucidated, with some studies having separately reported beta cell-protective effects of eNAMPT. eNAMPT exists in structurally and functionally distinct monomeric and dimeric forms. Dimerisation is essential for the NAD-biosynthetic capacity of NAMPT. Monomeric eNAMPT does not possess NAD-biosynthetic capacity and may exert distinct NAD-independent effects. This study aimed to fully characterise the structure-functional effects of eNAMPT on pancreatic beta cell functional mass and to relate these to beta cell failure in type 2 diabetes. Methods CD-1 mice and serum from obese humans who were without diabetes, with impaired fasting glucose (IFG) or with type 2 diabetes (from the Body Fat, Surgery and Hormone [BodyFatS&H] study) or with or at risk of developing type 2 diabetes (from the VaSera trial) were used in this study. We generated recombinant wild-type and monomeric eNAMPT to explore the effects of eNAMPT on functional beta cell mass in isolated mouse and human islets. Beta cell function was determined by static and dynamic insulin secretion and intracellular calcium microfluorimetry. NAD-biosynthetic capacity of eNAMPT was assessed by colorimetric and fluorescent assays and by native mass spectrometry. Islet cell number was determined by immunohistochemical staining for insulin, glucagon and somatostatin, with islet apoptosis determined by caspase 3/7 activity. Markers of inflammation and beta cell identity were determined by quantitative reverse transcription PCR. Total, monomeric and dimeric eNAMPT and nicotinamide mononucleotide (NMN) were evaluated by ELISA, western blot and fluorometric assay using serum from non-diabetic, glucose intolerant and type 2 diabetic individuals. Results eNAMPT exerts bimodal and concentration- and structure-functional-dependent effects on beta cell functional mass. At low physiological concentrations (~1 ng/ml), as seen in serum from humans without diabetes, eNAMPT enhances beta cell function through NAD-dependent mechanisms, consistent with eNAMPT being present as a dimer. However, as eNAMPT concentrations rise to ~5 ng/ml, as in type 2 diabetes, eNAMPT begins to adopt a monomeric form and mediates beta cell dysfunction, reduced beta cell identity and number, increased alpha cell number and increased apoptosis, through NAD-independent proinflammatory mechanisms. Conclusions/interpretation We have characterised a novel mechanism of beta cell dysfunction in type 2 diabetes. At low physiological levels, eNAMPT exists in dimer form and maintains beta cell function and identity through NAD-dependent mechanisms. However, as eNAMPT levels rise, as in type 2 diabetes, structure-functional changes occur resulting in marked elevation of monomeric eNAMPT, which induces a diabetic phenotype in pancreatic islets. Strategies to selectively target monomeric eNAMPT could represent promising therapeutic strategies for the treatment of type 2 diabetes.

scholarly journals ER stress increases store-operated Ca2+ entry (SOCE) and augments basal insulin secretion in pancreatic beta cells

2020 ◽  
Vol 295 (17) ◽  
pp. 5685-5700
Author(s):  
Irina X. Zhang ◽  
Jianhua Ren ◽  
Suryakiran Vadrevu ◽  
Malini Raghavan ◽  
Leslie S. Satin
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Beta Cell ◽  
Er Stress ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Cell Function ◽  
Critical Role ◽  
Beta Cell Apoptosis

Type 2 diabetes mellitus (T2DM) is characterized by impaired glucose-stimulated insulin secretion and increased peripheral insulin resistance. Unremitting endoplasmic reticulum (ER) stress can lead to beta-cell apoptosis and has been linked to type 2 diabetes. Although many studies have attempted to link ER stress and T2DM, the specific effects of ER stress on beta-cell function remain incompletely understood. To determine the interrelationship between ER stress and beta-cell function, here we treated insulin-secreting INS-1(832/13) cells or isolated mouse islets with the ER stress–inducer tunicamycin (TM). TM induced ER stress as expected, as evidenced by activation of the unfolded protein response. Beta cells treated with TM also exhibited concomitant alterations in their electrical activity and cytosolic free Ca2+ oscillations. As ER stress is known to reduce ER Ca2+ levels, we tested the hypothesis that the observed increase in Ca2+ oscillations occurred because of reduced ER Ca2+ levels and, in turn, increased store-operated Ca2+ entry. TM-induced cytosolic Ca2+ and membrane electrical oscillations were acutely inhibited by YM58483, which blocks store-operated Ca2+ channels. Significantly, TM-treated cells secreted increased insulin under conditions normally associated with only minimal release, e.g. 5 mm glucose, and YM58483 blocked this secretion. Taken together, these results support a critical role for ER Ca2+ depletion–activated Ca2+ current in mediating Ca2+-induced insulin secretion in response to ER stress.

scholarly journals MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus

Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 534
Author(s):  
Jamie M. R. Tarlton ◽  
Steven Patterson ◽  
Annette Graham
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Lipid Metabolism ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Cell Function ◽  
Therapeutic Strategies ◽  
Predictive Analysis

Alterations in lipid metabolism within beta cells and islets contributes to dysfunction and apoptosis of beta cells, leading to loss of insulin secretion and the onset of type 2 diabetes. Over the last decade, there has been an explosion of interest in understanding the landscape of gene expression which influences beta cell function, including the importance of small non-coding microRNA sequences in this context. This review sought to identify the microRNA sequences regulated by metabolic challenges in beta cells and islets, their targets, highlight their function and assess their possible relevance as biomarkers of disease progression in diabetic individuals. Predictive analysis was used to explore networks of genes targeted by these microRNA sequences, which may offer new therapeutic strategies to protect beta cell function and delay the onset of type 2 diabetes.

scholarly journals Arginase 2 and Polyamines in Human Pancreatic Beta Cells: Possible Role in the Pathogenesis of Type 2 Diabetes

2021 ◽  
Vol 22 (22) ◽  
pp. 12099
Author(s):  
Lorella Marselli ◽  
Emanuele Bosi ◽  
Carmela De Luca ◽  
Silvia Del Guerra ◽  
Marta Tesi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreas Development ◽  
Tissue Specific

Arginase 2 (ARG2) is a manganese metalloenzyme involved in several tissue specific processes, from physiology to pathophysiology. It is variably expressed in extra-hepatic tissues and is located in the mitochondria. In human pancreatic beta cells, ARG2 is downregulated in type 2 diabetes. The enzyme regulates the synthesis of polyamines, that are involved in pancreas development and regulation of beta cell function. Here, we discuss several features of ARG2 and polyamines, which can be relevant to the pathophysiology of type 2 diabetes.

DPP-4 is expressed in human pancreatic beta cells and its direct inhibition improves beta cell function and survival in type 2 diabetes

2018 ◽  
Vol 473 ◽  
pp. 186-193 ◽  
Author(s):  
Marco Bugliani ◽  
Farooq Syed ◽  
Flavia M.M. Paula ◽  
Bilal A. Omar ◽  
Mara Suleiman ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Direct Inhibition

scholarly journals The Dynamic Roles of Visfatin and Obestatin Serum Concentration in Pancreatic Beta Cells Dysfunction (HOMA-beta) and Insulin Resistance (HOMA-IR) in Centrally Obese Men

2012 ◽  
Vol 4 (1) ◽  
pp. 43
Author(s):  
Bayu Winata Putera ◽  
Cynthia Retna Sartika ◽  
Andi Wijaya
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Cell Dysfunction ◽  
Pancreas Cell

BACKGROUND: Obesity is a major health problem in the world today. Obesity is closely associated with insulin resistance and type 2 diabetes. Epidemiological studies have shown that obese persons are in a state of insulin resistance, however, most of them do not progress to type 2 diabetes. This occurs because the beta cell function is still good enough for maintaining normal glucose level. Obestatin and visfatin are cytokines that are known to have a role in beta cell function. The aim of this study was to assess the relationship between visfatin and obestatin and Homeostasis Model Assessment of beta cell function (HOMA-β) and Homeostasis Model Assessment of insulin resistance (HOMA-IR).METHODS: This was a cross-sectional study involving 80 central obesity men with waist circumference >90 cm, age 30-65 years old. Visfatin and obestatin were measured by ELISA method. Beta pancreas cell dysfunction and insulin resistance were calculated by HOMA model.RESULTS: Our study showed a correlation between visfatin and HOMA-β (r=0.244 and p = 0.029) and visfatin with HOMA-IR (r=0.287 and p=0.001) and no correlation was found between obestatin with HOMA-β (r=0.010 and p=0.990) and obestatin with HOMA-IR (r=0.080 and p=0.480). We also found visfatin and obestatin concentrations were fluctuative depending on the measurements of the waist circumferences.CONCLUSIONS: High visfatin and low obestatin concentration were independently associated with increased beta pancreas cell dysfunction and insulin resistance.KEYWORDS: obesity. visfatin, obestatin, beta cell dysfunction (HOMA-β), insulin resistance (HOMA-IR)

scholarly journals Alpha and Beta Cell Dysfunction Improves With Effective Insulin Therapy in Treatment Naive Type 2 Diabetes - a Prospective Observational Study

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A466-A466
Author(s):  
Jayanthy Ramesh ◽  
Ashok Chakravarthy Makineni ◽  
Madhubabu Mudimela ◽  
Srivalli Madhira
Keyword(s):  
Type 2 Diabetes ◽  
Beta Cell ◽  
Insulin Therapy ◽  
Islet Cell ◽  
Cell Function ◽  
Beta Cell Dysfunction ◽  
Newly Diagnosed ◽  
C Peptide ◽  
Cell Dysfunction

Abstract Abstract: Type 2 diabetes mellitus is characterized by insulin resistance and progressive beta cell decline. Elevated glucagon levels and impaired incretin axis also contribute to the poor glycemic status. Early intensive glycemic control, reduces long-term vascular complications and may preserve β-cell function. Clinical studies of effect of early insulin therapy on combined alpha and beta cell function are lacking. Objective: To determine the effect of early insulin therapy on combined alpha and beta cell dysfunction (islet cell dysfunction) in newly diagnosed type 2 diabetes. Methods: 56 newly diagnosed type 2 diabetes patients, attending the endocrinology OPD at a tertiary teaching hospital were enrolled in this treatment related follow up study after institutional ethical committee clearance, conducted between May 2017 to December 2018. Patients with HbA1C > 8.5% to <12.5% (n=56) were included in the study. Metabolic (FPG, PPG, HbA1c), and Hormonal parameters (plasma glucagon levels,fasting and 2 hour mixed meal stimulated C peptide and levels) were assessed both at baseline and after 6 months of insulin treatment. Initiating dose of insulin was 0.5 U/kg/day and the dose was titrated according to FPG and 2 hr PPG in order to maintain glycemic goals as per ADA standards. Results: The study included 56 subjects with mean age of 41.24 ± 5.64 years and a mean BMI of 25.5 kg/m2. At the end of 6 months of the study, a significant reduction in the mean FPG, PPG, HbA1C were observed,[FPG (139±14.47 mg/dl), PPG (179.89 ± 19.42mg/dl),HbA1c (7.54± 0.63%)] as compared to baseline mean FPG, (216.30 ± 42.35 mg/dl),2 hour PPG (338.44 ±62.89 mg/dl), HbA1C (10.39 ± 1.56 %) (p <0.001). Baseline glucagon levels were high (197.68± 49.09 pg/ml), and were significantly reduced at 6 months of insulin therapy (107.06±49.09 pg/ml).(p <0.001). In comparison to the baseline a significant increase in both fasting (0.73±0.27 ng/ml) and stimulated c-peptide (1.54±1.02 ng/ml) (p<0.001) levels was observed at end of the study. Conclusion: Combined alpha and beta cell (Islet) dysfunction prevails in newly diagnosed T2DM. And early insulin therapy significantly improves both these defects. The documentation of this novel beneficial effect on islet cell dysfunction in our study strengthens the concept of early insulin therapy in newly diagnosed Type 2 diabetes patients.

scholarly journals Butyrate Protects Pancreatic Beta Cells from Cytokine-Induced Dysfunction

2021 ◽  
Vol 22 (19) ◽  
pp. 10427
Author(s):  
Michala Prause ◽  
Signe Schultz Pedersen ◽  
Violeta Tsonkova ◽  
Min Qiao ◽  
Nils Billestrup
Keyword(s):  
Beta Cell ◽  
Beta Cells ◽  
Beta Cell Function ◽  
Pancreatic Beta Cells ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Beta Cell Dysfunction ◽  
Beta Cell Proliferation ◽  
Cell Dysfunction ◽  
Mouse Islets

Pancreatic beta cell dysfunction caused by metabolic and inflammatory stress contributes to the development of type 2 diabetes (T2D). Butyrate, produced by the gut microbiota, has shown beneficial effects on glucose metabolism in animals and humans and may directly affect beta cell function, but the mechanisms are poorly described. The aim of this study was to investigate the effect of butyrate on cytokine-induced beta cell dysfunction in vitro. Mouse islets, rat INS-1E, and human EndoC-βH1 beta cells were exposed long-term to non-cytotoxic concentrations of cytokines and/or butyrate to resemble the slow onset of inflammation in T2D. Beta cell function was assessed by glucose-stimulated insulin secretion (GSIS), gene expression by qPCR and RNA-sequencing, and proliferation by incorporation of EdU into newly synthesized DNA. Butyrate protected beta cells from cytokine-induced impairment of GSIS and insulin content in the three beta cell models. Beta cell proliferation was reduced by both cytokines and butyrate. Expressions of the beta cell specific genes Ins, MafA, and Ucn3 reduced by the cytokine IL-1β were not affected by butyrate. In contrast, butyrate upregulated the expression of secretion/transport-related genes and downregulated inflammatory genes induced by IL-1β in mouse islets. In summary, butyrate prevents pro-inflammatory cytokine-induced beta cell dysfunction.

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