Potentially synergistic effects of melatonin and metformin in alleviating hyperglycaemia: a comprehensive review

2021 ◽  
Vol 4 (4) ◽  
pp. 522-550
Author(s):  
Adrita Banerjee ◽  
Aindrila Chattopadhyay ◽  
Debasish Bandyopadhyay
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Synergistic Effects ◽  
Redox Status ◽  
Protein Glycation ◽  
Ros Generation ◽  
High Blood Glucose ◽  
High Level

High level of glucose is hazardous for organisms since it leads to lipid peroxidation, protein glycation and free radical generation. Insulin can lower the high blood glucose by promoting cell’s glucose up-taking. Thus, the impeded insulin secretion in type 1-diabetes and insensitivity of cells to insulin in type 2-diabetes cause hyperglycaemia. Hyperglycaemia impairs mitochondrial function of pancreas to trigger ROS generation. The malfunctional mitochondria cause endoplasmic reticulum to produce misfolded non-functional insulin, finally leading to diabetes. Melatonin, the mitochondria targeted antioxidant, provides protection against diabetes by multiple ways. These include balancing cellular redox status, lowering blood glucose level by modulating metabolic pathways and, finally protecting cells/organelles from high glucose induced injury. Moreover, this indoleamine preserves pancreatic physiological normalcy to facilitate insulin secretion. Thus, melatonin can effectively mitigate diabetes and diabetic complications. Metformin, the most prescribed medicine for type 2-diabetes, has similar antidiabetic activities as melatonin. Both the molecules share similar pathways to preserve stress-stricken pancreas and other organs, whereas, melatonin also potentiates the actions of metformin. The potentially synergistic actions of melatonin and metformin are expected and we strongly recommend a combined therapeutic application of these two molecules for treatment of diabetes.

scholarly journals Transcription factor 7-like 2 (TCF7L2): a culprit gene in Type 2 Diabetes Mellitus

2021 ◽  
Vol 24 (4) ◽  
pp. 371-376
Author(s):  
A. Jan ◽  
H. Jan ◽  
Z. Ullah
Keyword(s):  
Type 2 Diabetes ◽  
Transcription Factor ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Pancreatic Beta Cell ◽  
Genetic Research ◽  
Wnt Signaling Pathway ◽  
Diabetes Type 2 ◽  
Ethnic Population

The genetics of Type 2 diabetes a complex metabolic disorder, characterized by decreased insulin secretion and insulin resistance resulting in impaired blood glucose homeostasis remains enigma for geneticists. In 2006 an important step while finding genetic causes of diabetes type 2 was identification of transcription factor 7-like 2 (TCF7L2) gene an important marker in predisposition of type 2 diabetes in almost all ethnic population. Recent genetic research identifies numerous novel type 2 diabetes susceptible genes among these genes TCF7L2 is considered as gang head and emerged as the most promising types 2 diabetes causing gene. Risk variants in TCF7L2 effects pancreatic beta cell development and insulin secretion by influencing Wnt Signaling pathway. Genetic variants in TCF7L2 confer risk for type 2 diabetes by altering expression of transcription factor (which has key role in blood glucose regulation) in pancreas. The purpose of this paper is to evaluate type 2 diabetes susceptible gene the TCF7L2 and to present a comprehensive review of studies carried out worldwide in different ethnic population on association of TCF7L2 polymorphism with type 2 diabetes.

Sitagliptin: A DPP-4 Inhibitor for the Treatment of Type 2 Diabetes Mellitus

2011 ◽  
Vol 3 ◽  
pp. CMT.S6227 ◽  
Author(s):  
Kathryn MS Johnson ◽  
Kathleen Schurr
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetes Therapy ◽  
High Blood Glucose ◽  
Adverse Side Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels

Type 2 diabetes mellitus (T2DM) has become an epidemic, with worldwide projections indicating that more than 336 million people will be afflicted with the disease by 2030. T2DM is characterized by inappropriately high blood glucose levels due to a deficiency in insulin secretion, action, or both. Despite the horrific complications that occur with chronic elevations of blood glucose levels, less than half of those with T2DM do not maintain proper glycemic control. Sitagliptin (Januvia, Merck and Co., Whitehouse Station, New Jersey) is a novel diabetes therapy approved for use in the U.S. and Europe. This small molecule inhibits the activity of DPP-4, a peptidase that degrades the glucoregulatory hormone GLP-1. Sitagliptin increases glucoregulation in individuals with T2DM both as a monotherapy and in combination with other antihyperglycemic drugs, with a low risk of adverse side effects.

scholarly journals The impact of dietary protein restriction on insulin secretion and action

1999 ◽  
Vol 58 (3) ◽  
pp. 647-653 ◽  
Author(s):  
Mark J. Holness
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Insulin Action ◽  
Synergistic Effects ◽  
Protein Restriction ◽  
Dependent Diabetes Mellitus ◽  
Organ Systems ◽  
The Impact

The goal of this review is to develop the hypothesis, and review the evidence, that protein restriction, through synergistic effects on multiple organ systems predisposes to loss of normal regulation of fuel homeostasis that plays the central role in the development of type 2 (non-insulin-dependent) diabetes mellitus. The ability of insulin to regulate glucose production and disposal varies between individuals. These differences, together with the various compensatory mechanisms that are invoked to attempt to normalize fuel homeostasis, are of fundamental importance in the development and clinical course of type 2 diabetes mellitus. Protein deprivation impacts on both insulin secretion and insulin action. These effects may persist even when a diet containing adequate protein is presented subsequently. Data are presented that suggest that protein restriction results in an impaired ability of pancreatic β-cells to compensate adequately for the defect in insulin action in insulin-resistant individuals. This persistent impairment of insulin secretion resulting from protein restriction predisposes to loss of glucoregulatory control and impaired insulin action after the subsequent imposition of a diabetogenic challenge. This inability to maintain the degree of compensatory hyperinsulinaemia necessary to prevent loss of glucose tolerance may have relevance to the increased incidence of diabetes on changing from a nutritionally-poor diet to a Western diet, and to the hypothesis that some cases of type 2 diabetes in adulthood may be related to poor early nutrition.

scholarly journals L-Tryptophan Suppresses Rise in Blood Glucose and Preserves Insulin Secretion in Type-2 Diabetes Mellitus Rats

2012 ◽  
Vol 58 (6) ◽  
pp. 415-422 ◽  
Author(s):  
Tomoko INUBUSHI ◽  
Norio KAMEMURA ◽  
Masataka ODA ◽  
Jun SAKURAI ◽  
Yutaka NAKAYA ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Insulin Secretion ◽  
Blood Glucose

scholarly journals Do descendants of families contribute to type 2 diabetes mellitus?

2020 ◽  
Vol 9 (4) ◽  
pp. 303
Author(s):  
Fatma Nuraisyah ◽  
Solikhah Solikhah ◽  
Rochana Ruliyandari
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Family History ◽  
Venous Blood ◽  
Public Health Problem ◽  
High Level ◽  
Random Level

Diabetes is a public health problem in Indonesia that has been increasing in recent decades. Screening for diabetes was usually identified as pregnant women, adolescents, adults, children, older and obesity, while based on investigation descendent was yet. This cross-sectional study aimed to know the random level blood glucose of family history type 2 diabetes mellitus (T2DM). The target group for screening was people with a family history in one of their descent of T2DM with age >20 years in Kulon Progo, DIY, Indonesia. We conducted a detection of random level blood glucose from a venous blood sample. A high level of blood glucose was diagnosed when random blood glucose reaches ≥200 mg/dl. The participant with high level of blood glucose was 29.0%, while borderline blood glucose (≥110-199 mg/dl) was revealed 38.7% of 15.3% subject indicated with mother history. Descendant screening of family history T2DM is early detected respondent with high glucose level and reduced the severe complication.

scholarly journals Synergistic Effects of Nateglinide and Meal Administration on Insulin Secretion in Patients with Type 2 Diabetes Mellitus

2000 ◽  
Vol 85 (3) ◽  
pp. 1081-1086 ◽  
Author(s):  
Leonard Keilson ◽  
Sergio Mather ◽  
Yulia H. Walter ◽  
Siva Subramanian ◽  
James F. McLeod
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Plasma Glucose ◽  
Synergistic Effects ◽  
Peak Effect ◽  
Serious Adverse Events ◽  
Event Rates ◽  
Oral Doses ◽  
Dose Dependent

Abstract This study assessed the synergistic effects of nateglinide (a nonsulfonylurea d-phenylalanine derivative) and meals on insulin secretion in 24 patients with type 2 diabetes. Oral doses of 60 and 180 mg or 120 and 240 mg were administered to two cohorts of subjects 10 min before meals (or fasting) three times daily for 7 days, with washout intervals between treatment periods. Dose-dependent increases in plasma insulin occurred, with the peak effect within 2 h after treatment. Significantly greater insulin secretion was observed when nateglinide was taken before a meal compared to nateglinide given in the fasted state or in response to just the meal. Nateglinide lowered plasma glucose concentrations significantly vs. placebo at all doses, and doses of 120 and 240 mg were more effective than 60 mg (P < 0.05). Adverse event rates were similar for nateglinide and placebo, and no hypoglycemic episodes or serious adverse events were reported during the study. Nateglinide (120 mg) was the maximum effective dose in this study and was shown to be a safe and well tolerated therapy for control of mealtime glucose excursions in patients with type 2 diabetes. Results indicate that a synergistic interaction occurs between nateglinide and elevated mealtime plasma glucose concentrations to stimulate insulin secretion.

scholarly journals The relationships between glucose variability and renal function in type 2 diabetes patients on basal-bolus insulin therapy

2015 ◽  
Vol 18 (4) ◽  
pp. 66-71 ◽  
Author(s):  
Vadim V. Klimontov ◽  
Natalia E. Myakina
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Blood Glucose ◽  
Insulin Therapy ◽  
Glucose Variability ◽  
High Blood Glucose ◽  
Interstitial Glucose ◽  
Bolus Insulin ◽  
Basal Bolus

Aim. To assess the relationship of glucose variability (GV) and renal function in patients with type 2 diabetes on basal-bolus insulin therapy.Materials and methods. We observed 101 females with type 2 diabetes, aged 47–79 years, with a glomerular filtration rate (GFR) 30 mL/min/1.73 m2. Insulin was combined with metformin in 45 of these women. The mean glucose and standard deviation, continuous overlapping net glucose action, lability index, J-index, low blood glucose index (LBGI), high blood glucose index (HBGI), M-value and mean absolute glucose (MAG) were calculated based on the results of blinded continuous glucose monitoring. The prevalence of episodes of low interstitial glucose (3.9 and 2.8 mmol/L) of at least 20-min duration was estimated.Results. Patients with a GFR of 30–44 mL/min/1.73 m2 had significantly lower HBGI, J-index, MAG and M-value compared with those with better filtration (all p 0.05); LBGI was not dependent on GFR. The GFR values were weakly and positively correlated with HBGI, J-index, M-value and MAG. Multiple regression analysis showed that GFR is an independent predictor of MAG (p = 0.04). No significant differences were found in the prevalence of episodes of low interstitial glucose between patients with different GFR ranges.Conclusions. GV parameters are related to renal function in type 2 diabetic women on basal-bolus insulin therapy. Patients with stage 3b chronic kidney disease have reduced GV, predominantly in the hyperglycaemic band, compared with those with better filtration.

scholarly journals Saliva 1,5-anhydroglucitol is associated with early-phase insulin secretion in Chinese patients with type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002199
Author(s):  
Lingwen Ying ◽  
Chaohui Jian ◽  
Xiaojing Ma ◽  
Kun Ge ◽  
Wei Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Area Under The Curve ◽  
Chinese Patients ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
C Peptide

IntroductionSaliva collection is a non-invasive test and is convenient. 1,5-anhydroglucitol (1,5-AG) is a new indicator reflecting short-term blood glucose levels. This study aimed to explore the relationship between saliva 1,5-AG and insulin secretion function and insulin sensitivity.Research design and methodsAdult patients with type 2 diabetes who were hospitalized were enrolled. Based on blood glucose and C-peptide, homeostasis model assessment 2 for β cell secretion function, C-peptidogenic index (CGI), △2-hour C-peptide (2hCP)/△2-hour postprandial glucose (2hPG), ratio of 0–30 min area under the curve for C-peptide and area under the curve for glucose (AUCCP30/AUCPG30), and AUC2hCP/AUC2hPG were calculated to evaluate insulin secretion function, while indicators such as homeostasis model assessment 2 for insulin resistance were used to assess insulin sensitivity.ResultsWe included 284 subjects (178 men and 106 women) with type 2 diabetes aged 20–70 years. The saliva 1,5-AG level was 0.133 (0.089–0.204) µg/mL. Spearman’s correlation analysis revealed a significantly negative correlation between saliva 1,5-AG and 0, 30, and 120 min blood glucose, glycated hemoglobin A1c, and glycated albumin (all p<0.05), and a significantly positive association between saliva 1,5-AG and CGI (r=0.171, p=0.004) and AUCCP30/AUCPG30 (r=0.174, p=0.003). The above correlations still existed after adjusting for age, sex, body mass index, and diabetes duration. In multiple linear regression, saliva 1,5-AG was an independent factor of CGI (standardized β=0.135, p=0.015) and AUCCP30/AUCPG30 (standardized β=0.110, p=0.020).ConclusionsSaliva 1,5-AG was related to CGI and AUCCP30/AUCPG30 in patients with type 2 diabetes.Trial registration numberChiCTR-SOC-17011356.

scholarly journals KORELASI INDEKS 20/(C-PEPTIDE PUASA×GLUKOSA DARAH PUASA) DENGAN HOMA-IR UNTUK MENILAI RESISTENSI INSULIN DIABETES MELITUS TIPE 2

2016 ◽  
Vol 38 (4) ◽  
pp. 155
Author(s):  
Elsi Kelana ◽  
Ellyza Nasrul ◽  
Rismawati Yaswir ◽  
Desywar Desywar
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Blood Glucose ◽  
Pearson Correlation ◽  
Fasting Blood Glucose ◽  
Biological Response ◽  
Fasting Insulin ◽  
C Peptide

AbstrakResistensi insulin merupakan penurunan respons biologis jaringan terhadap insulin dalam kadar normal. Pada DM tipe 2 terjadi resistensi dan gangguan sekresi insulin. Terdapat indeks baru 20/(C-peptide puasa x glukosa darah puasa) untuk menilai resistensi sekaligus gangguan sekresi insulin. Penelitian bertujuan membuktikan korelasi indeks 20/(C-peptide puasa x glukosa darah puasa) dengan HOMA-IR untuk menilai resistensi insulin pada DM tipe 2 di RSUP. Dr. M. Djamil Padang. Dengan menggunakan sampel darah dari pasien, kadar glukosa darah puasa, insulin puasa dan C-peptide puasa ditentukan. Data yang diperoleh kemudian dianalisis menggunakan korelasi Pearson. Hasil penelitian menunjukkan rerata kadar glukosa puasa 9,83 (3,53) mmol/L [177 (63,54) mg/dL], insulin puasa 10,58 (3,61) μU/L, dan C-peptide puasa 0,97 (0,29) nmol/L dan terdapat korelasi yang sangat kuat dan bermakna secara statistik (p<0,0001) antara indeks 20/(C-peptide puasa x glukosa darah puasa) dengan HOMA-IR (r= -0,838). Dapat disimpulkan bahwa indeks 20/(C-peptide puasa x glukosa darah puasa) dan HOMA–IR berkorelasi kuat untuk menilai resistensi insulin pada DM tipe 2 di RSUP. Dr. M. Djamil Padang.AbstractInsulin resistance is a decrease of biological response of the tissues to the normal level of insulin. In type 2 diabetes, there is resistance and impaired of insulin secretion. There is a new index available to assess resistance and impaired of insulin secretion all at once, with the formula 20/(fasting C-peptide x fasting blood glucose). This study aimed to prove the correlation of this new index to the HOMA-IR (Homeostasis model assesment of insulin resistance) in type 2 diabetes at Dr.M.Djamil Padang hospital. Level of fasting glucose, fasting insulin and fasting C-peptide of blood were measured, followed by statistical data analysis using Pearson correlation test.The result showed the mean of fasting blood glucose, fasting insulin and fasting C-peptide were 9.83 (3.53) mmol/L[177 (63.54) mg/dl], 10.58 (3.61) μU/L, and 0.97 (0.29) nmol/L respectively.There was a strong and statistically significant correlation (p<0.0001) found between the new index and the HOMA-IR ( r= -0.838). To be concluded, the index 20/(fasting C-peptide x fasting blood glucose) and HOMA-IR was strongly correlated to assess insulin resistance in type 2 diabetes at Dr. M. Djamil Padang hospital.

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