scholarly journals Herbal Medicines Targeting the Improved β-Cell Functions and β-Cell Regeneration for the Management of Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-32
Author(s):  
Akurange Sujeevi Dammadinna Wickramasinghe ◽  
Pabasara Kalansuriya ◽  
Anoja Priyadarshani Attanayake
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Herbal Medicines ◽  
Cell Regeneration ◽  
Model Assessment ◽  
Β Cells ◽  
Β Cell ◽  
Cell Functions ◽  
Glucose Transporter 2 ◽  
Β Cell Function

There is an increasing trend of investigating natural bioactive compounds targeting pancreatic β-cells for the prevention/treatment of diabetes mellitus (DM). With the exploration of multiple mechanisms by which β-cells involve in the pathogenesis of DM, herbal medicines are gaining attention due to their multitasking ability as evidenced by traditional medicine practices. This review attempts to summarize herbal medicines with the potential for improvement of β-cell functions and regeneration as scientifically proven by in vivo/in vitro investigations. Furthermore, attempts have been made to identify the mechanisms of improving the function and regeneration of β-cells by herbal medicines. Relevant data published from January 2009 to March 2020 were collected by searching electronic databases “PubMed,” “ScienceDirect,” and “Google Scholar” and studied for this review. Single herbal extracts, polyherbal mixtures, and isolated compounds derived from approximately 110 medicinal plants belonging to 51 different plant families had been investigated in recent years and found to be targeting β-cells. Many herbal medicines showed improvement of β-cell function as observed through homeostatic model assessment-β-cell function (HOMA-β). Pancreatic β-cell regeneration as observed in histopathological and immunohistochemical studies in terms of increase of size and number of functional β-cells was also prominent. Increasing β-cell mass via expression of genes/proteins related to antiapoptotic actions and β-cell neogenesis/proliferation, increasing glucose-stimulated insulin secretion via activating glucose transporter-2 (GLUT-2) receptors, and/or increasing intracellular Ca2+ levels were observed upon treatment of some herbal medicines. Some herbal medicines acted on various insulin signaling pathways. Furthermore, many herbal medicines showed protective effects on β-cells via reduction of oxidative stress and inflammation. However, there are many unexplored avenues. Thus, further investigations are warranted in elucidating mechanisms of improving β-cell function and mass by herbal medicines, their structure-activity relationship (SAR), and toxicities of these herbal medicines.

scholarly journals Functional Status of Pancreatic α and β Cells in Type 2 Diabetes Mellitus Patients with Different Plasma Triglyceride Levels: A Retrospective Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Hang Guo ◽  
Chunlei Ma ◽  
Xiaoming Wu ◽  
Congqing Pan
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Density Lipoprotein ◽  
Plasma Triglyceride ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function

Objective. To investigate the functional status of pancreatic α and β cells in Type 2 diabetes mellitus (T2DM) patients with different plasma triglyceride (TG) levels. TG levels can be prognostic markers for T2DM. Methods. A total of 328 patients with T2DM were divided into three groups according to different TG levels: the TGL group: TG < 1.7 mmol/L; TGM group: 1.7 mmol/L ≤ TG < 2.3 mmol/L; and TGH group: TG ≥ 2.3 mmol/L. An oral glucose tolerance test (OGTT), insulin release test, and glucagon release test were performed in each patient. The changes of glucagon, glucagon/insulin ratio, early insulin secretion index ( Δ I 30 / Δ G 30 ), and area under the insulin curve (AUCI) were compared among each group. Also, the correlations between glucagon and pancreatic β-cell function, glycosylated hemoglobin (HbA1c), and other indices were analyzed. Results. With the increase of TG, the fasting and postprandial glucagon levels, the glucagon/insulin ratio, and the area under the glucagon curve (AUCG) presented an increasing trend. The homeostasis model assessment of insulin resistance (HOMA–IR) of the TGH group was significantly increased compared to the TGL and TGM groups. In addition to the increase in TG levels, the insulin sensitivity index (ISI), homeostasis model assessment for β-cell function index (HOMA-β), Δ I 30 / Δ G 30 , and AUCI displayed a reducing trend. Glucagon was negatively correlated with Δ I 30 / Δ G 30 , high-density lipoprotein (HDL), HOMA-β, body mass index (BMI), ISI, and AUCI ( P < 0.05 ) and positively correlated with fasting blood glucose (FPG), AUCG, HOMA-IR, HbA1c, duration, TG, low-density lipoprotein (LDL), and total cholesterol (TC) ( P < 0.05 ). Conclusion. Hypertriglyceridemia aggravated the dysfunction of pancreatic α and β cells. A reasonable control of the TG level makes it easier for blood glucose to reach the standard.

Longitudinal Glycaemic Profiles during Remission in 6q24-Related Transient Neonatal Diabetes Mellitus

2021 ◽  
Vol 94 (5-6) ◽  
pp. 229-234
Author(s):  
Yasuhiro Sato ◽  
Tsuyoshi Isojima ◽  
Kiyomi Takamiya ◽  
Kahoko Motoyama ◽  
Shigehiro Enkai ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Neonatal Diabetes ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Transient Neonatal Diabetes Mellitus ◽  
Glucose Intake ◽  
Β Cell Function ◽  
Transient Neonatal Diabetes

<b><i>Introduction:</i></b> Transient neonatal diabetes mellitus (TNDM) is a rare condition that is characterized by the presence of diabetes mellitus during the first 6 months of life and remission by 18 months of age. It usually relapses at a median age of 14 years. Hyperinsulinaemic hypoglycaemia is a relatively common complication during remission. Although β-cell function is reported to be impaired at relapse, the clinical course of glycaemic profiles during remission in patients with TNDM remains largely unknown. <b><i>Case Presentation:</i></b> Longitudinal glycaemic profiles were investigated annually from remission (185 days) to relapse (14.5 years) in a patient with TNDM due to paternal 6q24 duplication using the oral glucose tolerance test (glucose intake: 1.75 g/kg to a maximum of 75 g). The patient’s β-cell function and insulin sensitivity were assessed by calculating the insulinogenic index, homeostasis model assessment of β-cell function (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index, and Matsuda index. Early insulin response to glucose intake was impaired throughout remission, whereas fasting insulin and β-cell function by HOMA-β gradually increased in the first few years since remission, followed by a gradual decline in function. In contrast, HOMA-IR fluctuated and peaked at 6.5 years of age. <b><i>Conclusion:</i></b> This is the first report of annual longitudinal glycaemic profiles in a patient with 6q24-related TNDM during remission. We identified fluctuations in β-cell function and insulin resistance during remission.

miR-124-3p Down-Regulation Influences Pancreatic-β-Cell Function by Targeting Secreted Frizzled-Related Protein 5 (SFRP5) in Diabetes Mellitus

2021 ◽  
Vol 11 (4) ◽  
pp. 711-717
Author(s):  
Zhenhuan Jiang ◽  
Min Yang ◽  
Jianming Jin ◽  
Zhenqiang Song ◽  
Chenguang Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Cell Function ◽  
Luciferase Reporter ◽  
Pancreatic Β Cell ◽  
Β Cells ◽  
Β Cell ◽  
Pancreatic Β Cells ◽  
Down Regulation ◽  
Β Cell Function ◽  
Direct Target

Diabetes mellitus (DM) is a complex metabolic disease characterized by hyperglycemia, insulin resistance and pancreatic β-cell dysfunction. There are evidences showed that microRNAs (miRNAs) play important roles in DM. The purpose of our study was to determine the role of miR-124-3p in DM. Quantitative reverse transcription PCR (qRT-PCR) was applied to measure the level of miR- 124-3p in peripheral blood from healthy control patients and DM patients. Then we explored the effects of miR-124-3p inhibitor on the secretion of insulin of pancreatic β-cells. Moreover, we determined the effects of miR-124-3p inhibitor on the apoptosis and viability of pancreatic β-cells through flow cytometry and MTT assay. And we also used western blotting to detect the protein expression of cleaved-caspase3/pro-caspase3, and the activity of caspase3 was detected. In addition, we confirmed the direct target of miR-124-3p using Dual luciferase reporter assay. Our data showed that in the blood of DM patients, SFRP5 was significantly reduced, while miR-124-3p was increased significantly. Furthermore, we found that down-regulation of miR-124-3p increased total insulin content in INS-1 cells, enhanced insulin secretion in INS-1 cells. Furthermore, we revealed that miR-124-3p inhibitor enhanced INS-1 cell viability, decreased apoptosis of INS-1 cells, increased pro-caspase3 expression, decreased cleaved-caspase3 expression and caspase3 activity. In addition, we proved SFRP5 was a direct target of miR-124-3p in pancreatic β-cells. Moreover, SFRP5-siRNA reversed all the effects of miR-124-3p knockdown on pancreatic β-cells.

scholarly journals Coloured Rice Phenolic Extracts Increase Expression of Genes Associated with Insulin Secretion in Rat Pancreatic Insulinoma β-cells

2020 ◽  
Vol 21 (9) ◽  
pp. 3314
Author(s):  
Gideon Gatluak Kang ◽  
Nidhish Francis ◽  
Rodney Hill ◽  
Daniel LE Waters ◽  
Christopher L. Blanchard ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Β Cells ◽  
Β Cell ◽  
Cell Dysfunction ◽  
Glucose Transporter 2 ◽  
Expression Of Genes ◽  
Β Cell Function ◽  
The Impact ◽  
Phenolic Extracts

Glucose-induced oxidative stress is associated with the overproduction of reactive oxygen species (ROS), which may dysregulate the expression of genes controlling insulin secretion leading to β-cell dysfunction, a hallmark of type 2 diabetes mellitus (T2DM). This study investigated the impact of coloured rice phenolic extracts (CRPEs) on the expression of key genes associated with β-cell function in pancreatic β-cells (INS-1E). These genes included glucose transporter 2 (Glut2), silent mating type information regulation 2 homolog 1 (Sirt1), mitochondrial transcription factor A (Tfam), pancreatic/duodenal homeobox protein 1 (Pdx-1) and insulin 1 (Ins1). INS-1E cells were cultured in high glucose (25 mM) to induce glucotoxic stress conditions (HGSC) and in normal glucose conditions (NGC-11.1 mM) to represent normal β-cell function. Cells were treated with CRPEs derived from two coloured rice cultivars, Purple and Yunlu29-red varieties at concentrations ranged from 50 to 250 µg/mL. CRPEs upregulated the expression of Glut2, Sirt1 and Pdx-1 significantly at 250 µg/mL under HGSC. CRPEs from both cultivars also upregulated Glut2, Sirt1, Tfam, Pdx-1 and Ins1 markedly at 250 µg/mL under NGC with Yunlu29 having the greatest effect. These data suggest that CRPEs may reduce β-cell dysfunction in T2DM by upregulating the expression of genes involved in insulin secretion pathways.

scholarly journals Exercise and dexamethasone oppositely modulate β-cell function and survival via independent pathways in 90% pancreatectomized rats

2006 ◽  
Vol 190 (2) ◽  
pp. 471-482 ◽  
Author(s):  
Soo Bong Choi ◽  
Jin Sun Jang ◽  
Sang Mee Hong ◽  
Dong Wha Jun ◽  
Sunmin Park
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Cell Mass ◽  
Signaling Cascade ◽  
Β Cells ◽  
Β Cell ◽  
Cell Functions ◽  
Igf I ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Long-term dexamethasone (DEX) treatment is well known for its ability to increase insulin resistance in liver and adipose tissues leading to hyperinsulinemia. On the other hand, exercise enhances peripheral insulin sensitivity. However, it is not clear whether DEX and/or exercise affect β-cell mass and function in diabetic rats, and whether their effects can be associated with the modulation of the insulin/IGF-I signaling cascade in pancreatic β-cells. After an 8-week study, whole body glucose disposal rates in 90% pancreatectomized (Px) and sham-operated male rats decreased with a high dose treatment of DEX (0.1mg DEX/kg body weight/day)(HDEX) treatment, while disposal rates increased with exercise. First-phase insulin secretion was decreased and delayed by DEX via the impairment of the glucose-sensing mechanism in β-cells, while exercise reversed the impairment of first-phase insulin secretion caused by DEX, suggesting ameliorated β-cell functions. However, exercise and DEX did not alter second-phase insulin secretion except for the fact that HDEX decreased insulin secretion at 120 min during hyperglycemic clamp in Px rats. Unlike β-cell functions, DEX and exercise exhibited increased pancreatic β-cell mass in two different pathways. Only exercise, through increased proliferation and decreased apoptosis, increased β-cell mass via hyperplasia, which resulted from an enhanced insulin/IGF-I signaling cascade by insulin receptor substrate 2 induction. By contrast, DEX expanded β-cell mass via hypertrophy and neogenesis from precursor cells, rather than increasing proliferation and decreasing apoptosis. In conclusion, the improvement of β-cell function and survival via the activation of an insulin/IGF-I signaling cascade due to exercise has a crucial role in preventing the development and progression of type 2 diabetes.

Plasma Secretagogin is Increased in Individuals with Glucose Dysregulation

2019 ◽  
Author(s):  
Chao Yang ◽  
Hua Qu ◽  
Xiaolan Zhao ◽  
Yingru Hu ◽  
Jiayao Xiong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Cell Function ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cells ◽  
Β Cell ◽  
Β Cell Function ◽  
First Phase Insulin Secretion

Abstract Objective Secretagogin, a Ca2+ binding protein, is one of the most abundant proteins in pancreatic β-cells and is critical for maintaining the structural integrity and signaling competence of β-cells. This study seeks to assess the concentrations of plasma secretagogin in participants with prediabetes (pre-DM) and newly diagnosed type 2 diabetes (T2DM) and to explore its relationship to parameters of glucose and lipid metabolism, first-phase insulin secretion, insulin resistance and pancreatic β-cell function. Materials and Methods A total of 126 eligible subjects were divided into three groups: a normal glucose tolerance (NGT, n=45), a pre-DM (n=30), and a T2DM (n=51) group. An intravenous glucose tolerance test (IVGTT) was performed, and clinical and biochemical parameters were measured for all subjects. Results Plasma secretagogin levels were significantly higher in both pre-DM and T2DM patients compared with NGT subjects and were highest in the T2DM group. Correlation analysis showed that plasma secretagogin levels were positively correlated with fasting plasma glucose, postchallenge plasma glucose (2hPG), HbA1c and body mass index (BMI) but were not correlated with waist-hip ratio, blood pressure, lipid profiles, fasting serum insulin, homeostasis model assessment for insulin resistance, homeostasis model assessment for β-cell function and first-phase insulin secretion indicators. Multiple logistic regression analysis revealed that 2hPG and BMI were independent predictors for elevation of plasma secretagogin concentrations. Conclusions Increased circulating secretagogin might be a molecular predictor for early diagnosis of diabetes. Further studies are needed to confirm this finding and explore the role of secretagogin in obesity.

scholarly journals Homeostasis Model Assessment (HOMA) and M Value in Daily Profile of Glucose

2018 ◽  
Vol 1 (1) ◽  
pp. 1-7 ◽  
Author(s):  
Koji Ebe ◽  
Hiroshi Bando ◽  
Tetsuo Muneta ◽  
Masahiro Bando ◽  
Yoshikazu Yonei
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cell Function ◽  
Immunoreactive Insulin ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Β Cell Function

Background: Low Carbohydrate Diet (LCD) and Calorie Restriction (CR) have been on discussion for years. Authors have continued diabetic research about LCD, CR, Morbus (M) value and insulin secretion. In this study, homeostasis model assessment (HOMA) was investigated. Subjects and Methods: Subjects enrolled were 52 patients with type 2 diabetes mellitus (T2DM) (average 62.3 years). Methods included the measurement of fasting glucose and immunoreactive insulin (IRI), daily profile of blood glucose and M value. Results: The obtained data were as follows: average HbA1c 8.0%, average glucose of daily profile 222 mg/dL. Median data were M value 151, HOMA-R 1.07, HOMA-β 11.1. Divided into 4 groups due to M value, the levels of HOMA-R and HOMA-β in each group were 0.68, 1.08, 1.64, 1.38 and 16.9, 16.3, 10.2, 5.3, respectively. Significant correlation were observed between M value and HOMA-R (p<0.01), and between M value and HOMA-β (p<0.01). Discussion and Conclusion: As M value increases, HOMA-R increases and HOMA-β decreases. These findings suggested that diabetic patients would have insulin resistance and decreased β cell function correlated to the severity of diabetes, and that obtained results would become the basal data in this field, expecting the further development in the future research. Keywords: Type 2 diabetes mellitus (T2DM), Morbus value (M value), Homeostasis model assessment of insulin resistance (HOMA-R), Homeostasis model assessment of β cell function (HOMA-β), Daily profile of blood glucose, Immunoreactive insulin (IRI)

scholarly journals Pericytes contribute to the islet basement membranes to promote beta-cell gene expression

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lina Sakhneny ◽  
Alona Epshtein ◽  
Limor Landsman
Keyword(s):  
Gene Expression ◽  
Cell Function ◽  
Basement Membranes ◽  
Cell Physiology ◽  
Β Cells ◽  
Β Cell ◽  
Cell Clustering ◽  
Β Cell Function ◽  
Cell Gene Expression ◽  
Glucose Stimulated Insulin Secretion

Abstractβ-Cells depend on the islet basement membrane (BM). While some islet BM components are produced by endothelial cells (ECs), the source of others remains unknown. Pancreatic pericytes directly support β-cells through mostly unidentified secreted factors. Thus, we hypothesized that pericytes regulate β-cells through the production of BM components. Here, we show that pericytes produce multiple components of the mouse pancreatic and islet interstitial and BM matrices. Several of the pericyte-produced ECM components were previously implicated in β-cell physiology, including collagen IV, laminins, proteoglycans, fibronectin, nidogen, and hyaluronan. Compared to ECs, pancreatic pericytes produce significantly higher levels of α2 and α4 laminin chains, which constitute the peri-islet and vascular BM. We further found that the pericytic laminin isoforms differentially regulate mouse β-cells. Whereas α2 laminins promoted islet cell clustering, they did not affect gene expression. In contrast, culturing on Laminin-421 induced the expression of β-cell genes, including Ins1, MafA, and Glut2, and significantly improved glucose-stimulated insulin secretion. Thus, alongside ECs, pericytes are a significant source of the islet BM, which is essential for proper β-cell function.

scholarly journals Leptin Levels, β-Cell Function, and Insulin Sensitivity in Families with Congenital and Acquired Generalized Lipoatropic Diabetes1

1998 ◽  
Vol 83 (2) ◽  
pp. 503-508
Author(s):  
Victor C. Pardini ◽  
Ivana M. N. Victória ◽  
Selma M. V. Rocha ◽  
Danielle G. Andrade ◽  
Aline M. Rocha ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Temporal Relationship ◽  
Cell Function ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Β Cell ◽  
Insulin Levels ◽  
Β Cell Function ◽  
Plasma Leptin ◽  
Specific Insulin

Lipoatropic diabetes (LD) designates a group of syndromes characterized by diabetes mellitus with marked insulin resistance and either a localized or generalized absence of adipose tissue. In this study, we evaluated plasma leptin levels in subjects with congenital generalized lipoatropic diabetes (CGLD, n = 11) or acquired generalized lipoatropic diabetes (AGLD, n = 11), and assessed correlations between leptin levels and estimations of insulin secretion and insulin sensitivity using homeostasis model assessment (HOMA). Leptin levels were 0.86 ± 0.32, 1.76 ± 0.78, and 6.9 ± 4.4 ng/mL in subjects with CGLD, AGLD, and controls (n = 19), respectively (ANOVA P &lt; 0.0001). Specific insulin levels were 154 ± 172, 177 ± 137 and 43 ± 22 pmol/L, respectively (P &lt; 0.0001). Insulin sensitivity was significantly decreased in both groups with LD (P&lt; 0.0001), whereas HOMA β-cell function was not significantly different when compared with controls. Leptin levels were significantly correlated with body mass index, insulin levels, and HOMA β-cell function, and inversely correlated with insulin sensitivity in control subjects but not in subjects with generalized LD. In conclusion, decreased leptin levels were observed in subjects with generalized LD, with a trend towards lower levels in the acquired than in the congenital form (P = 0.06). The temporal relationship between the decrease in leptin levels and the development of lipoatrophy should be investigated in at-risk young relatives of subjects with the acquired forms to assess the usefulness of leptin levels as a marker of lipoatrophy.

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