Disturbances In Insulin Secretion Research Articles

HCV affects KATP channels through GnT-IVa-mediated N-glycosylation of GLUT2 on the surface of pancreatic β-cells leading to impaired insulin secretion.

To explore the mechanism of insulin secretion dysfunction in pancreatic beta cells induced by N-glycosylation mediated by an infection from the hepatitis C virus (HCV). Min6 cell models infected with HCV and stimulated with glucose were constructed. Meanwhile, an HCV-infected animal model and a type 2 diabetes mellitus (T2DM) rat model were constructed. Glucose uptake in the Min6 cells was detected, and insulin secretion was detected by ELISA. Flow cytometry, immunofluorescence staining, Western blotting, RT-qPCR, and lectin blotting were used to detect the expression levels of related proteins and mRNA, as well as the level of N-glycosylation. HE staining was used to observe the pathological changes in the pancreatic tissue, and an oral glucose tolerance test (OGTT) was used to evaluate the glucose tolerance of the rats. Compared with the NC group, the expression levels of GnT-IVa, GLUT2, galectin-9, and voltage-dependent calcium channel 1.2 (Cav1.2) were significantly downregulated in the HCV-infected group. The ATP-sensitive potassium channel (KATP) component proteins SUR1 and Kir6.2 were significantly upregulated, while intracellular glucose intake and insulin secretion decreased, N-glycosylation levels and ATP levels significantly decreased, and the overexpression of GnT-IVa reversed the effect of the HCV infection. However, treatment with the glycosylation inhibitor kifunensine (KIF) or the KATP channel activator diazine (Dia) reversed the effects of the overexpression of GnT-IVa. In the animal experiments, HE staining revealed serious pathological injuries in the pancreatic tissue of the HCV-infected rats, with decreased glucose tolerance and glycosylation levels, decreased insulin secretion, downregulated expression of GnT-IVa, GLUT2, and Cav1.2, and upregulated expression of SUR1 and Kir6.2. The overexpression treatment of GnT-IVa or the KATP channel antagonist miglinide reversed the effects of HCV. HCV infection inhibits GLUT2 N-glycosylation on the pancreatic β cell surface by downregulating the expression of GnT-IVa and then activates the KATP pathway, which ultimately leads to disturbances in insulin secretion.

Lifestyle Modification Therapy in Diabetes Disease: A Review Article

Introduction: Diabetes mellitus (DM) is a metabolic disease characterized by high blood glucose levels (hyperglycemia) resulting from disturbances in insulin secretion, insulin action or both. Insulin is a hormone produced by pancreatic beta cells, which is needed to utilize glucose from digested food. Comprehensive care is taken to treat patients with either prediabetes or diabetes. Diabetes management includes lifestyle interventions along with pharmacologic therapy and routine blood glucose monitoring. So that a decrease in blood glucose can occur and can be stable for a long time. Discussion:Lifestyle modification is an economical treatment that saves costs to prevent or delay the onset of diabetes. On the other hand, nutritional management provided by a dietitian is also recommended. Moderate weight loss goals are an important component of diabetes prevention and treatment, as large body weight can increase blood glucose levels, and can also have an increasing impact on blood pressure and cholesterol levels. Weight loss can be achieved through a balanced diet, with total control of calories and free carbohydrates. However, for diabetic patients following a low-carbohydrate diet, they should be informed about possible side effects such as hypoglycemia, headaches and constipation. Other studies have suggested the consumption of complex dietary fiber and whole grains to improve blood sugar control. Greater adherence to diet combined with light physical activity was associated with a lower likelihood of diabetes after adjusting for various factors. Conclusion:Lifestyle modification is a fairly cost-effective treatment to prevent or delay the onset of diabetes, with a risk reduction of about 58% in 3 years. It is strongly recommended by the ADA that patients with IGT, IFG or HbA1C levels of 5.7-6.4% be counseled on lifestyle changes such as diet and exercise. On the other hand, nutritional management provided by a dietitian is also recommended.

A combination of melatonin and moderate-intensity aerobic exercise improves pancreatic beta-cell function and glycemic homeostasis in type 2 diabetic model of animals

Nocturnal melatonin secretion is important for preservation of ß-cell mass and function. Knowing that type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia caused by the elevated resistance of peripheral tissues to insulin, reduction in pineal melatonin and disturbances of insulin secretion by pancreatic ß-cells. In this context, exercise is considered one of the most valuable non-pharmacological approaches for treatment of T2DM. Considering the beneficial role of melatonin on glycemic metabolism in physical exercise, we investigated the effects of moderate-intensity aerobic exercise plus melatonin on glycemic homeostasis, the morphology and architecture of pancreas in spontaneous T2DM animals [Goto-Kakizaki (GK) rats]. The results confirmed that melatonin alone reduced the mass of epididymal white adipose tissue (WAT); however, only the combination of melatonin and physical exercise significantly reduced caloric intake, body weight, WAT and improved glucose tolerance and insulin sensitivity in T2DM rats. This combination also reduced apoptosis of cells in pancreatic islets. We observed either melatonin or the combination was able to reduce insulinemia. However, only the combination improved the morphology of the pancreatic islets. Thus, we conclude that in GK rats, melatonin plays a crucial role in the functionality of the pancreas to improve insulin sensitivity of peripheral tissues and, consequently, to maintain the glucose homeostasis. In addition, the combination is more efficiency to improve glucose tolerance and integrity of pancreatic islets in GK rats than melatonin alone.

Laporan Kasus: Kegoyangan Gigi Pada Pasien disertai Diabetes Mellitus

Diabetes Mellitus is a metabolic disorder characterized by an increase in blood glucose levels (hyperglycemia) due to disturbances in insulin secretion and insulin action. Diabetes mellitus (DM) is a disease characterized by high blood glucose levels, because the body cannot release or use insulin adequately. There are many factors that trigger or aggravate periodontitis, including plaque accumulation, calculus (tartar), and systemic factors such as diabetes mellitus. Objective: To explain that there is a close relationship between elevated blood glucose levels and periodontitis. Case Description: A 77 year old woman presented with a loose left upper tooth and pain during eating. The patient admitted to having a history of systemic disease, namely diabetes mellitus. Intra oral examination was found on 27th grade 3 luxation, 6 mm gingival recession, 4 mm probing depth, debris around the teeth, oral hygiene tends to be poor. The therapy provided is in the form of education on the effect of diabetes mellitus on teeth and the condition of the oral cavity in general, as well as the importance of maintaining health and food consumption so that blood sugar conditions are controlled. Conclusion: Periodontal disease can be affected by DM. Periodontitis is one of the manifestations of DM in the oral cavity. The severity of periodontitis can result from an increase in blood glucose levels.

Potentialof Red Dragon Fruit Juices (Hylocereus polyrhizus) to the Brain Histopathologic Repair in Rats (Rattus norvegicus) with Diabetes

Diabetes mellitus is a metabolic disease characterized by hyperglycemia due to disturbances in insulin secretion, insulin action, or both. The purpose of this study was to analyze the effect of the red dragon fruit juice (Hylocereus polyrhizus) to repair brain organ histopathologic female wistar rats (Rattus norvegicus Wistar strain) with diabetes. This research is a true experiment research with randomized control - group pretest - posttest design and were conducted at the in Vivo Laboratory of Wijaya Kusuma University Surabaya. Twenty five female wistar rats were randomly divided into 5 groups, normal rats group KA (without alloxan induction), diabetic rats group KB (alloxan induction and without given any red dragon fruit juices), treatment group KC (alloxan induction + 2 gr/2,5ml of red dragon fruit juices), treatment group KD (alloxan induction + 4 gr/2,5ml of red dragon fruit juices) and treatment group KE (alloxan induction + 8 gr/2,5ml of red dragon fruit juices). The study was conducted during the period of 16 days with standard feeding adaptations for 7 days. On day 16, all the rats were terminated. Glucose meter is used to measure the levels of blood glucose in rats. Histopathologic observation of rat brain tissue using a microscope Olympus CX21 with Haematoksilin eosin (HE) staining. The results showed the best dose of red dragon fruit juices to decrease blood glucose levels compare between KB and KE with significance p-value = 0.000 (α < 0.05), the blood glucose levels decreased in diabetic rats significantly between KB and KE also decreased in rat brain tissue necrosis with p-value = 0.000 (α <0.05).

Uji Efektivitas Beras Herbal Forte terhadap Penurunan Kadar Glukosa Darah Pasien Diabetes Melitus Tipe 2 (Study of the Herbal Rice Forte Effectiveness on Decreasing Blood Glucose of Diabetes Mellitus Type 2 Patient)


 Diabetes mellitus is metabolic diseases characterized by hyperglycemia caused by disturbances in insulin secretion or insulin activity. Herbal Forte Rice is rice synthetic material composed of main purple sweet potato and corn flour. It contains antioksidan, fiber, resistant starch and having moderate glycemic index. This study aimed to determine the effectivity of Herbal Forte Rice on decreasing blood glucose levels of patients type 2 DM. It used a cross-over design, the role of research subjects was both as control and treatment groups. Total sample of this research consisted of 60 samples. The treatment group was given Herbal Forte Rice for 7 days in 2 consecutive meals, while the control group did not receive any intervention. The results showed the average level of Fasting Blood Glucose (FBG) beginning and end of the treatment group 179.76 mg/dL and 138.7 mg/dL; FBG beginning and end of the control 180.87 mg/dL and 187.63 mg/dL; 2 hours post prandial Blood Glucose (2hppBG) levels of beginning and end of the treatment group 284.37 mg/dL and 183.8 mg/dL; 2hppBG levels beginning and end of the control 280.57 mg/dL and 284.13 mg/dL. This study concludes that Herbal Forte Rice effective on decreasing blood glucose levels of patients type 2 DM.
 
 Keywords: diabetes mellitus, Rice Herbal Forte, GDP and GD2PP

Disturbances in insulin secretion and subclinical inflammation in normoglycemic women with a history of pregnancy complicated by gestational diabetes mellitus

Disturbances in insulin secretion and subclinical inflammation in normoglycemic women with a history of pregnancy complicated by gestational diabetes mellitus

Adipokines and β-cell dysfunction in normoglycemic women with previous gestational diabetes mellitus.

An increased risk of developing type 2 diabetes in women with a history of gestational diabetes mellitus(gestational diabetes mellitus - GDM) may be associated with increased insulin resistance and subclinical inflammation. However, approximately half of women with previous GDM (pGDM) do not develop diabetes. These women were the population of focus in the present study. The aim of the study was to assess β-cell function, insulin resistance, and the levels of pro- and anti inflammatory adipokines in normoglycemic women with pGDM. A study group included 199 women with pGDM; the mean time after delivery was 7.4 years. A control group included 50 women without pGDM. All patients underwent an oral glucose tolerance test (OGTT) with the assessment of glycemia and insulinemia, β-cell function (HOMA-%β), and insulin resistance (HOMA-IR), as well as the levels of soluble tumor necrosis factor α receptor (sTNF-α-R2), interleukin 6 (IL-6), adiponectin, and visfatin. Normal glucose tolerance was found in 113 women with pGDM (56.8%; the NGT-GDM[+] group) and in 44 control subjects (88.0%). In comparison with controls, the NGT-GDM[+] group had significantly higher glycemia in the OGTT and significantly lower HOMA-%β values, with comparable HOMA-IR and body mass index values. The NGT-GDM(+) group was shown to have significantly higher levels of sTNF-α-R2 and IL-6, with similar adiponectin and visfatin levels. Normoglycemic women with a history of GDM are characterized by concomitant disturbances in insulin secretion and subclinical inflammation, with normal body weight and insulin sensitivity. It is not known whether these disturbances were present before a GDM-complicated pregnancy or whether they were induced by pregnancy.

The Hijacking of Cellular Signaling and the Diabetes Epidemic: Mechanisms of Environmental Disruption of Insulin Action and Glucose Homeostasis

The burgeoning epidemic of metabolic disease causes significant societal and individual morbidity and threatens the stability of health care systems around the globe. Efforts to understand the factors that contribute to metabolic derangements are critical for reversing these troubling trends. While excess caloric consumption and physical inactivity superimposed on a susceptible genetic background are central drivers of this crisis, these factors alone fail to fully account for the magnitude and rapidity with which metabolic diseases have increased in prevalence worldwide. Recent epidemiological evidence implicates endocrine disrupting chemicals in the pathogenesis of metabolic diseases. These compounds represent a diverse array of chemicals to which humans are exposed via multiple routes in adulthood and during development. Furthermore, a growing ensemble of animal- and cell-based studies provides preclinical evidence supporting the hypothesis that environmental contaminants contribute to the development of metabolic diseases, including diabetes. Herein are reviewed studies linking specific endocrine disruptors to impairments in glucose homeostasis as well as tying these compounds to disturbances in insulin secretion and impairments in insulin signal transduction. While the data remains somewhat incomplete, the current body of evidence supports the hypothesis that our chemically polluted environment may play a contributing role in the current metabolic crisis.

Efficacious and safe control of glycemia using Apidra insulin

Diabetes mellitus (DM) is a stably growing pathology leading to micro- and macrovascular complications. Despite high potential of medicamentaltherapy for DM its efficacy needs to be further improved. Uncompensated postprandial hyperglycemia is known to be responsible for many diabeticcomplications. Moreover, it by itself aggravates disturbances of insulin secretion through the toxic effect of glucose. Insulin therapy remains a principaltool for the treatment of DM. Its efficiency was greatly improved with the advent of fast-acting insulin analogs obtained by reducing stability of hexamers.Insulin glulysine (Apidra) is the fastest-acting analog licensed for the treatment of DM1 and DM2 in adult patients in 2004 (FDA, EMEA) andin children above 6 years in 2008 (EMEA). A characteristic feature of this analog is the absence of Zn2+ in its molecule that substitutes polysorbate-20 acting as a surfactant and providing additional protection of monomers from denaturation.

Selective amino acid deficiency in patients with impaired glucose tolerance and type 2 diabetes

Introduction Amino acids are important modulators of glucose metabolism, insulin secretion and insulin sensitivity. However, little is known about the changes in amino acid metabolism in patients with diabetes. Patients and methods The circulating amino acid levels were determined in 17 patients with type 2 diabetes, 17 individuals with impaired glucose tolerance (IGT), and 14 control subjects. Results Total amino acid concentrations were 2850 ± 57 µmol/l in patients with type 2 diabetes, 2980 ± 77 µmol/l in individuals with IGT, and 2886 ± 74 µmol/l in control subjects ( p = 0.38). Patients with type 2 diabetes exhibited significant reductions in the concentrations of gamma-aminobutyric acid (GABA), arginine, glutamine and phosphoethanolamine ( p < 0.05), whereas valine levels were higher than in controls ( p = 0.008). In IGT subjects, GABA levels were reduced, while tyrosine concentrations were increased ( p < 0.05). The plasma levels of essential amino acids were positively related to fasting and post-challenge glucose levels, fasting C-peptide, HOMA insulin resistance and fasting glucagon levels ( p < 0.05). Conclusions Total amino acid levels are similar in patients with diabetes, IGT subjects and controls, but the individual levels of several amino acids differ significantly between these groups. These alterations may contribute to the disturbances in insulin secretion and action in diabetic patients and may provide a rationale for offering specific amino acid supplementations to diabetic patients.

Early disturbances in insulin secretion in the development of type 2 diabetes mellitus

After a short description of normal glucose homeostasis, recent findings in relation to insulin release in three groups with a high risk of future development of type 2 diabetes are described. Hyperglycemic clamps in subjects with impaired glucose tolerance (IGT) clearly indicate that pancreatic beta cell function is decreased, in addition to the decreased insulin sensitivity. In women with former gestational diabetes mellitus (GDM), insulin release is also lower than in controls. In Caucasian first-degree relatives (FDRs) with normal glucose tolerance, various studies have shown that beta cell function is lower than in controls, while on the average insulin sensitivity is normal. This implies that beta cell function is disturbed earlier in subjects at risk of developing diabetes than is often appreciated. In the near future, the genetic studies currently underway will presumably unravel the pathogenesis of disturbances both in insulin secretion and in insulin action, in type 2 diabetes mellitus.

Disturbances in insulin secretion and sensitivity in women with the polycystic ovary syndrome

Insulin resistance, defined as a diminished effect of a given dose of insulin on glucose homeostasis, is a highly prevalent feature of women with PCOS. Insulin resistance in PCOS is closely associated with an increase in truncal-abdominal fat mass, elevated free fatty acid levels, increased androgens, particularly free testosterone through reduced SHBG levels, and anovulation. The causes for insulin resistance in PCOS are still unknown. One line of evidence suggests that an increase in truncal-abdominal fat mass and subsequently increased free fatty acid levels induce insulin resistance in women with PCOS. Increased effects of corticosteroids and a relative reduction in oestrogen and progesterone seem to be involved in the aberrant body fat distribution. Conversely, there are also results supporting primary, genetic target cell defects as a cause of insulin resistance in PCOS. An explanation for these seemingly contradictory results could be that the group of women with PCOS is heterogeneous with respect to the primary event in carbohydrate/insulin disturbances. Also insulin secretion in PCOS is characterized by heterogeneity. At one end of the spectrum is a large subgroup of mainly obese women with reduced insulin secretion, which appears to result from failure of the beta cells to compensate for insulin resistance in susceptible women, resulting in glucose intolerance and NIDDM. In the insulin-resistant patients with normal glucose tolerance, most of the hyperinsulinaemia is probably due to secondarily increased insulin secretion and decreased insulin degradation. However, a component of the increased first-phase insulin release is not due to measurable insulin resistance. Notably, this is also found in lean women with normal insulin sensitivity, and is not reversed after weight reduction, in contrast to the findings for insulin resistance. The implications of this enhanced insulin release are not fully clear, but it may tentatively be associated with carbohydrate craving and subsequently increased risks for development of obesity and insulin resistance. It may represent a primary disturbance of insulin secretion in PCOS or may be associated with the perturbed steroid balance in anovulation. The insulin-androgen connection in PCOS appears to be amplified by several different mechanisms, notably in both directions, the initiating event probably varying between individuals. Thus insulin increases the biological availability of potent steroids, primarily testosterone, through the suppression of SHBG synthesis. Insulin is also involved as a progonadotrophin in ovarian steroidogenesis, with the possible net result of interfering with ovulation and/or increasing ovarian androgen production in states of hyperinsulinaemia. Conversely, testosterone may indirectly contribute to insulin resistance through facilitating free fatty acid release from abdominal fat, but perhaps also through direct muscular effects at higher serum levels. It seems likely that this constitution, presumably genetic, would provide evolutionary advantages in times of limited nutrition, given the energy-saving effects of insulin resistance. Hypothetically, hyperinsulinaemia (primary) could provide a stimulus to ensure intake of nourishment, but unlimited food supplies could in some cases initiate a vicious 'anabolic' circle, in which several of the proposed amplifying mechanisms between insulin and androgens--in both directions--could take part.

Non-insulin dependent diabetes mellitus: defects in insulin secretion.

NIDDM is a heterogeneous disorder, characterized by defects in insulin secretion as well as in insulin action. Several pathophysiological mechanisms are involved in the development of disturbances in insulin secretion. One of the histological features of islets of NIDDM patients is the deposition of amyloid-like material. Accumulation of amyloid over many years can lead to slowly progressive disruption of islet architecture and possibly to some of the abnormalities in insulin secretion, as found in NIDDM patients. Loss of pulsatility is the earliest detectable abnormality of insulin secretion in the disease, either as a specific early defect or as a disturbance caused by minimally elevated blood glucose levels. Although it has been shown that maximum insulin release is decreased by 50% in NIDDM, the B-cell sensitivity to glucose appears to be normal. Coregulatory factors such as prostaglandins do not play a major role in the derangements of insulin secretion in NIDDM. An imbalance between stimulatory and inhibitory endorphins, or in sympathetic tone may be of more importance. Hyperglycaemia by itself has a deleterious effect on insulin release, and may perpetuate the disturbances of insulin secretion.

Beta-endorphin infusion restores acute insulin responses to glucose in type-2 diabetes mellitus.

To address the possibility that an abnormality in pancreatic beta-endorphin activity might contribute to abnormal insulin secretion in diabetes mellitus, we studied the effects of beta-endorphin infusion on islet function in diabetic patients. The iv infusion of human beta-endorphin at a dose of 0.5 mg/h for 2 h in type-2 non-insulin-dependent diabetic patients (n = 12) raised plasma insulin and glucagon levels and slightly but significantly lowered plasma glucose concentrations. beta-Endorphin infusion also resulted in reappearance of a clear-cut acute insulin response to glucose, while second phase insulin release was increased and glucose disposal accelerated. Acute insulin and glucagon responses to arginine were not increased by beta-endorphin, suggesting that the effect of the opioid on the B cells of the diabetic patients is specific for glucose. An intraislet abnormality of opioid peptides action and/or secretion may play a role in the disturbances of insulin secretion in patients with type-2 diabetes mellitus.