Insulin Secretion Action Research Articles

THE EFFECTIVENESS OF SUPPORTIVE SELF CARE EDUCATION USING THE EDUCATION BOOKLET TOWARD THE ABILITY EARLY DETECTION OF HYPOGLYCEMIA AND HYPERGLYCEMIA OF DIABETES MELLITUS PATIENTS AT RSUD BIMA IN 2017

Abstract: Diabetes Mellitus (DM) is a metabolic disorder caused by a disruption of insulin secretion or impaired insulin activity resulting in the occurrence of hyperglycemia and cells not getting enough glucose for energy. Hypoglycemia and Hyperglycemia in DM patients is an acute complication of DM that can occur repeatedly and can aggravate DM disease can even cause death. Prevalence of hypoglycemia is quite high, about 90% of patients receiving insulin therapy have experienced hypoglycemia. The high prevalence and the magnitude risk of hypoglycemia and severe hyperglycemia is closely relate to the behavior of DM patients in managing the disease, especially behavior and the ability in early detection of hypoglycemic conditions and hyperglycemia. The development of hypoglycemia and hyperglycemia in more severe circumstances can be prevented by increased ability to control blood glucose and early detection of hypoglycemia and hyperglycemia by enhancing early detection of risk factors or causes, interpretation of symptoms of hypoglycemia and early hyperglycemia so that more severe complications can be prevented. The purpose of this study is to analyze the The effectiveness of Supportive Self Care Education using the Educational Booklet toward the ability Early Detection of Hypoglycemia and Hyperglycemia of Diabetes Mellitus Patients at RSUD Bima in 2017. This type of research is quantitative research using pre experiment design with two group pretest and posttest approach. Independent T test was used to analyse the data. The study had been conducted for 9 weeks, from September to October 2017. The results show that supportive self-care education with educational booklet increase the ability of detection hypoglicemia and hyperglycemia that are indcated by the increasing ability of early detection of hypoglycemia and hyperglycemia in treatment group compared to group control (p = 0.000; α = 0.05). The findings are expected to improve nursing care in DM patients, as one of the independent interventions that can be done by nurses and to increase knowledge related to the concept of self-care education in nursing perspective based on self-care orem nursing theory and to be able to provide education with appropriate methods, prevent acute hypoglycemic and hyperglycemic emergencies.Keywords: Educational, Booklet, Hypoglicemia, Hyperglicemia.

Functional Maturation and In Vitro Differentiation of Neonatal Porcine Islet Grafts

There is a strong rationale to pursue the use of neonatal porcine islets (NPIs) as an unlimited source of islets for clinical xenotransplantation. Because NPIs are composed of immature insulin producing beta (ß) cells and ductal precursor cells, they provide an ideal model to examine culture conditions to enhance ß cell proliferation and/or ß cell neoformation from ductal cells. In an attempt to optimize the potential of NPIs as a source of ß cell grafts, we used an in vitro differentiation protocol and measured its effect on the functional maturation and differentiation of NPIs. Pancreata from 1- to 3-day-old neonatal pigs were digested and cultured in standard Ham's F10 media for 5 days. Each independent preparation was then further cultured in Dulbecco's modified Eagle medium nutrient mixture-F12 differentiation media containing growth factors added in a stepwise fashion, or cultured in control Ham's F10 media. After 20 days in culture, islets were assessed for insulin secretory capacity, cellular composition, gene expression, and metabolic activity after transplantation in immunodeficient mice with diabetes. Compared with control islets, differentiated islets exhibited a significantly higher proportion of endocrine cells, proliferating cell nuclear antigen double positive ß cells, and an enhanced glucose-stimulated insulin secretory activity. Mice transplanted with differentiated islets had significantly lower blood glucose values at weeks 18 and 20 compared with nondifferentiated controls and were shown to be more glucose tolerant. Culturing NPIs in a 20-day stepwise differentiation media increases the proportion of endocrine cells and augments both in vitro and in vivo function of the islets.

In vitro and in vivo antidiabetic activity of isolated fraction of Prosopis cineraria against streptozotocin-induced experimental diabetes: A mechanistic study.

A rapidly increasing incidence of Diabetes mellitus throughout the world is a major concern in both developed and developing countries and the drawbacks associated with currently available treatments led to switching researcher's attention towards naturopathy. Since ancient time, herbal plants have been traditionally used for the treatment of diabetes as they consider to be less toxic and free from side effects than synthetic ones. In our previous studies, we had isolated two new compounds (Methyl 5-tridecyloctadec-4-enoate and Nonacosan-8-one), together with three known compounds (Lupeol, β-sitosterol and Stigmasterol) from chloroform fraction of stem bark of P. cineraria (CfPc). The present study aimed to determine the in vivo and in vivo antidiabetic activity of CfPc in streptozotocin induced experimental diabetes and also evaluated their possible mode of action. CfPc was orally administrated to STZ (55 mg/kg b.wt) induced diabetic rats at the doses of 50 and 100 mg/kg b.wt for 21 days. Treatment of CfPc significantly (p < 0.05) lowered the level of blood glucose, glycosylated hemoglobin and also restored body weight, liver glycogen content and serum insulin level in diabetic rats in a dose-dependent manner. A significant (p < 0.05) reduction in serum lipid profile markers and elevation in HDL-C after treatment with CfPc, also signifying the protective effects of CfPc in diabetes-associated complications. In addition, CfPc also promoted a significant inhibition of α-amylase enzyme activity with an IC50 value of 40.29 μg/ml. Results indicate that CfPc possess a potential in vitro and in vivo antidiabetic activity and this effect could be due to multitarget mode of action that includes antihyperglycemic, postprandial hypoglycemic, hypolipidemic and insulin secretory actions. Therefore, it could be used as a safer complementary drug in the management of diabetes and associated complications.

Antihyperglycemic property and insulin secreting activity of hydroalcoholic shoot extract of Thymus caramanicus Jalas: A wild predominant source of food additive in folk medicine

Thymus caramanicus Jalas is a plant that is widely used in the Iranian folk medicine; it serves as spices, tea, and herbal medicine. The present research was carried out to investigate its antidiabetic properties. Oral hydroalcoholic shoot extract of T. caramanicus Jalas (TCE; 300 and 500 mg/kg body weight) 30 min before glucose loading have be observed to improve oral glucose tolerance test in diabetic rats at 240 min. Daily TCE administration for 14 days also showed antihyperglycemic, antilipid peroxidative, antioxidant, and α-amylase inhibitory activities. Also, the TCE improved insulin release, lipid profile, liver and kidney function indices and decreased mRNA levels of sodium-glucose co-transporter 2 (SGLT2) and facilitated glucose transporter 2 (GLUT2) in kidney of diabetic rats. Medicinally, TCE contained important bioactive compounds, such as flavonoids (rutin, quercetin, and luteolin) and phenolic acids (rosmarinic and caffeic acids) leading to its adjusted use as a natural remedy in diabetes mellitus.

Anti-inflammatory and insulin secretory activity in experimental type-2 diabetic rats treated orally with magnesium.

Abstract Background Diabetes mellitus causes low-grade chronic inflammation which leads to the development of long-term complications. Oral magnesium (Mg) intake amongst other effects was reported to reduce the levels of inflammatory markers. This study investigated the anti-inflammatory and insulin secretory activities in experimental type-2 diabetic rats (n=32) orally treated with Mg. Methods Experimental type-2 diabetic rats were induced with high fat diet and alloxan (50 mg/kg, single i.p.) for over 10 weeks prior to the experimental procedures. Male Wistar rats were divided into 4 equal groups: control, untreated experimental diabetics, and experimental diabetics treated orally with either metformin (Met) (250 mg/kg), or Mg (250 mg/kg), respectively, for 14 days. The blood glucose (BG) levels were monitored before experimental induction of diabetes and thereafter on days 1, 7, 10, and 14, respectively. Serum insulin, C-reactive protein (CRP), interleukin-6 (IL-6), and lipid profile were assessed using laboratory kits while pancreatic beta cell function (BCF) and insulin resistance were estimated using homeostasis model assessment equations. Results Significant increase in the BG level was observed in all experimental diabetic groups on day 1 compared to controls. On day 14, BG, BCF, triglyceride, cholesterol, and low-density lipoprotein levels were increased while the high-density lipoprotein level was reduced in untreated diabetics compared to other groups. Insulin and insulin resistance were increased in all groups compared to control. Serum insulin and IL-6 were reduced while CRP was elevated in diabetic treated groups (Met and Mg) compared to untreated diabetics. Conclusions This study shows a hypoglycemic, lipid regulatory, insulin stimulatory, and anti-inflammatory effect of oral Mg treatment in experimental type-2 diabetic rats.

Protein-restriction diet during the suckling phase programs rat metabolism against obesity and insulin resistance exacerbation induced by a high-fat diet in adulthood

Protein restriction during the suckling phase can malprogram rat offspring to a lean phenotype associated with metabolic dysfunctions later in life. We tested whether protein-caloric restriction during lactation can exacerbate the effect of a high-fat (HF) diet at adulthood. To test this hypothesis, we fed lactating Wistar dams with a low-protein (LP; 4% protein) diet during the first 2 weeks of lactation or a normal-protein (NP; 23% protein) diet throughout lactation. Rat offspring from NP and LP mothers received a normal-protein diet until 60 days old. At this time, a batch of animals from both groups was fed an HF (35% fat) diet, while another received an NF (7% fat) diet. Maternal protein-caloric restriction provoked lower body weight and fat pad stores, hypoinsulinemia, glucose intolerance, higher insulin sensitivity, reduced insulin secretion and altered autonomic nervous system (ANS) function in adult rat offspring. At 90 days old, NP rats fed an HF diet in adulthood displayed obesity, impaired glucose homeostasis and altered insulin secretion and ANS activity. Interestingly, the LP/HF group also presented fat pad and body weight gain, altered glucose homeostasis, hyperleptinemia and impaired insulin secretion but at a smaller magnitude than the NP-HF group. In addition, LP/HF rats displayed elevated insulin sensitivity. We concluded that protein-caloric restriction during the first 14 days of life programs the rat metabolism against obesity and insulin resistance exacerbation induced by an obesogenic HF diet.

Insulin releasing effect of some pure compounds from Moringa oleifera on mice islets

The anti-diabetic activity of extracts, fractions and compounds of Moringa oleifera have been reported; however, several constituents from this well known medicinal plant are not yet screened for bio-perspecting role for diabetes. Current studies demonstrated the anti-diabetic properties of five chemical constituents of the plant viz, 4-hydroxyphenylacetonitrite (1), fluoropyrazine (3), methyl-4-hydroxybenzoate (4), vanillin (5), and 4-α-L-rhamnopyranosyloxybenzyl isothiocyanate (6) along with one related compound 3,4-dihydroxy benzonitrile (2) for the first time in vitro and in vivo. Furthermore, the mechanism of action of compounds was predicted by utilizing molecular docking with protein kinase A (PKA) and exchange protein activated by cAMP (Epac2A). The structure of compounds was elucidated by UV, IR, MS, and 1H NMR. The compounds 1, 3–5 induced significant insulin secretion at stimulatory (16.7 mM) glucose, but not at basal (3 mM) glucose concentration, and compound 3 seems to be the most active. Compounds 1, 3–5 showed dose-dependent insulin secretory activity with optimum response at 200 μM. In silico studies revealed that compound 3 has a noticeable electrostatic and hydrophobic interaction with protein kinase A (PKA). In vitro studies also showed that there was significant reduction of compounds 1–3 mediated insulin secretion in the presence of PKA inhibitor suggesting that there is a possible role of PKA signaling pathway on insulin secretion. Upon oral administration of 1, 3–5 to diabetic rats, compounds 1 and 3 significantly reduced blood glucose level in diabetic rats in a dose- and time-dependent manner. The oral glucose tolerance test in diabetic rats showed that compound 3 significantly enhanced plasma insulin and improved beta-cell function. In cytotoxicity assay, compounds 1, 3–5 did not show any toxic effect upto 200 μM. The insulin releasing characteristic of different constituents from M. oleifera conceivably correlate the lowering of blood glucose in in vivo diabetic rats by triggering glucose-induced insulin secretion from pancreatic islets possibly by PKA-mediated insulin secretory pathway.

A novel GLP-1/xenin hybrid peptide improves glucose homeostasis, circulating lipids and restores GIP sensitivity in high fat fed mice

Combined modulation of peptide hormone receptors including, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and xenin, have established benefits for the treatment of diabetes. The present study has assessed the biological actions and therapeutic efficacy of a novel exendin-4/xenin-8-Gln hybrid peptide, both alone and in combination with the GIP receptor agonist (DAla2)GIP. Exendin-4/xenin-8-Gln was enzymatically stable and exhibited enhanced insulin secretory actions when compared to its parent peptides. Exendin-4/xenin-8-Gln also possessed ability to potentiate the in vitro actions of GIP. Acute administration of exendin-4/xenin-8-Gln in mice induced appetite suppressive effects, as well as significant and protracted glucose-lowering and insulin secretory actions. Twice daily administration of exendin-4/xenin-8-Gln, alone or in combination with (DAla2)GIP, for 21-days significantly reduced non-fasting glucose and increased circulating insulin levels in high fat fed mice. In addition, all exendin-4/xenin-8-Gln treated mice displayed improved glucose tolerance, insulin sensitivity and metabolic responses to GIP. Combination therapy with (DAla2)GIP did not result in any obvious further benefits. Metabolic improvements in all treatment groups were accompanied by reduced pancreatic beta-cell area and insulin content, suggesting reduced insulin demand. Interestingly, body weight, food intake, circulating glucagon, metabolic rate and amylase activity were unaltered by the treatment regimens. However, all treatment groups, barring (DAla2)GIP alone, exhibited marked reductions in total- and LDL-cholesterol. Furthermore, exendin-4 therapy also reduced circulating triacylglycerol. This study highlights the positive antidiabetic effects of exendin-4/xenin-8-Gln, and suggests that combined modulation of GLP-1 and xenin related signalling pathways represents an exciting treatment option for type 2 diabetes.

Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in β-Cell Function and Survival.

Modulation of cholecystokinin (CCK) receptors has been shown to influence pancreatic endocrine function. We assessed the impact of the CCKA and CCKB receptor modulators, (pGlu-Gln)-CCK-8 and gastrin-17, respectively, on β-cell secretory function, proliferation and apoptosis and glucose tolerance, and investigating alterations of CCK and gastrin islet expression in diabetes. Initially, the presence of CCK and gastrin, and expression of their receptors were evidenced in β-cell lines and mouse islets. (pGlu-Gln)-CCK-8 and gastrin-17 stimulated insulin secretion from BRIN-BD11 and 1.1B4 β-cells, associated with no effect on membrane potential or [Ca]i. Only (pGlu-Gln)-CCK-8 possessed insulin secretory actions in isolated islets. In agreement, (pGlu-Gln)-CCK-8 improved glucose disposal and glucose-induced insulin release in mice. In addition, (pGlu-Gln)-CCK-8 evoked clear satiety effects. Interestingly, islet colocalization of CCK with glucagon was elevated in streptozotocin- and hydrocortisone-induced diabetic mice, whereas gastrin coexpression in α cells was reduced. In contrast, gastrin colocalization within β-cells was higher in diabetic mice, while CCK coexpression with insulin was decreased in insulin-deficient mice. (pGlu-Gln)-CCK-8 and gastrin-17 also augmented human and rodent β-cell proliferation and offered protection against streptozotocin-induced β-cell cytotoxicity. We highlight the direct involvement of CCKA and CCKB receptors in pancreatic β-cell function and survival.

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)

&#x0D; 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.&#x0D; &#x0D; Keywords: diabetes mellitus, Rice Herbal Forte, GDP and GD2PP&#x0D;

Atlantic salmon (Salmo salar) co-product-derived protein hydrolysates: A source of antidiabetic peptides

Large quantities of low-value protein rich co-products, such as salmon skin and trimmings, are generated annually. These co-products can be upgraded to high-value functional ingredients. The aim of this study was to assess the antidiabetic potential of salmon skin gelatin and trimmings-derived protein hydrolysates in vitro. The gelatin hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L exhibited significantly higher (p < 0.001) insulin and GLP-1 secretory activity from pancreatic BRIN-BD11 and enteroendocrine GLUTag cells, respectively, when tested at 2.5 mg/mL compared to hydrolysates generated with Alcalase 2.4L or Promod 144MG. The gelatin hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L showed significantly more potent (p < 0.01) DPP-IV inhibitory activity than those generated with Alcalase 2.4L or Promod 144MG. No significant difference was observed in the insulinotropic activity mediated by any of the trimmings-derived hydrolysates when tested at 2.5 mg/mL. However, the trimmings hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L exhibited significantly higher DPP-IV inhibitory (p < 0.05:Alcalase 2.4L and p < 0.01:Promod 144MG) and GLP-1 (p < 0.001, 2.5 mg/mL) secretory activity than those generated with Alcalase 2.4L or Promod 144MG. The salmon trimmings hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L when subjected to simulated gastrointestinal digestion (SGID) was shown to retain its GLP-1 secretory and DPP-IV inhibitory activities, in addition to improving its insulin secretory activity. However, the gelatin hydrolysate generated with Alcalase 2.4L and Flavourzyme 500L was shown to lose GLP-1 secretory activity following SGID. A significant increase in membrane potential (p < 0.001) and intracellular calcium (p < 0.001) by both co-product hydrolysates generated with Alcalase 2.4L and Flavourzyme 500L suggest that both hydrolysates mediate their insulinotropic activity through the KATP channel-dependent pathway. Additionally, by stimulating a significant increase in intracellular cAMP release (p < 0.05) it is likely that the trimmings-derived hydrolysate may also mediate insulin secretion through the protein kinase A pathway. The results presented herein demonstrate that salmon co-product hydrolysates exhibit promising in vitro antidiabetic activity.

Regulator of G-protein signaling Gbeta5-R7 is a crucial activator of muscarinic M3 receptor-stimulated insulin secretion

Regulator of G-protein signaling Gbeta5-R7 is a crucial activator of muscarinic M3 receptor-stimulated insulin secretion

Insulinotropic Activity of Standardized Methanolic Extracts of Ficus deltoidea from Seven Varieties.

Ficus deltoidea is a traditional medicinal plant that has been proven to show antidiabetic effects. This study focus is to assess the insulin secretion activity of Ficus deltoidea standardized methanolic extracts from seven independent varieties and mechanisms that underlie the insulin secretion action of the extracts. The cytotoxicity of Ficus deltoidea extracts was tested using viability assay. The insulin secretion assay was carried out by treating clonal BRIN BD11 cell line with standardized methanolic Ficus deltoidea extracts or glybenclamide. The clonal BRIN BD11 cell was also treated with insulin agonist and antagonist to elucidate the insulin secretion mechanism. Only the viability percentage for Ficus deltoidea var. kunstleri and intermedia was identified to be toxic at 500 and 1000 μg/ml (P<0.001). The insulin secretion for Ficus deltoidea var. deltoidea, angustifolia, and motleyana was dose-dependent; further evaluation suggested that Ficus deltoidea var. trengganuensis was involved in KATP-independent pathway. This study suggests that standardized methanolic extracts of Ficus deltoidea varieties have an insulinotropic effect on clonal BRIN BD11 cell line and can be utilized as a modern candidate of antidiabetic agents targeting the escalation for insulin secretion from pancreatic beta cells.

Oxytocin is present in islets and plays a role in beta-cell function and survival

Oxytocin is associated mainly with modulating reproductive function. However, studies suggest that oxytocin also plays a role in endocrine pancreatic function. In the present study, islet expression of oxytocin and its related receptor was confirmed in mouse islets as well as cultured rodent and human beta-cells. Oxytocin significantly stimulated glucose-induced insulin secretion from isolated mouse islets. Similar insulinotropic actions were also observed in rodent BRIN BD11 and human 1.1B4 beta-cells. Positive effects of oxytocin on insulin secretion were almost fully annulled by the oxytocin receptor antagonist, atosiban. In terms of mechanism of insulin secretory action, oxytocin had no effect on beta-cell membrane potential or cAMP generation, but did augment intracellular calcium concentrations. In vivo administration of oxytocin to mice significantly reduced overall blood glucose levels and increased plasma insulin concentrations in response to a glucose challenge. Oxytocin also had a modest, but significant, appetite suppressive effect. As expected, streptozotocin diabetic mice had marked loss of beta-cell area accompanied by increases in alpha-cell area, whilst hydrocortisone treatment increased beta-cell and overall islet areas. Both mouse models of diabetes presented with dramatically decreased percentage islet oxytocin co-localisation with insulin and increased co-localisation with glucagon. More detailed studies in cultured beta-cell lines revealed direct positive effects of oxytocin on beta-cell proliferation and protection against apoptosis. Together, these data highlight a potentially important role of islet-derived oxytocin and related receptor signalling pathways on the modulation of beta-cell function and survival.

Eriodictyol stimulates insulin secretion through cAMP/PKA signaling pathway in mice islets

Eriodictyol, a flavonoid isolated from Lyonia ovalifolia, was found to be the most potent insulin secretagogue in our preliminary studies. Here, we explored mechanism(s) of insulin secretory activity of eriodictyol in vitro and in vivo. Mice islets and MIN6 cells were incubated in basal and stimulatory glucose containing eriodictyol with or without agonist/antagonist. Secreted insulin and cAMP contents were measured using ELISA kits. K+- and Ca2+-channels currents were recorded with patch-clamp technique. Oral glucose tolerance test and plasma insulin was evaluated in non-diabetic and diabetic rats. Eriodictyol stimulated insulin secretion from mice islets and MIN6 cells only at stimulatory glucose concentrations with maximum effect at 200μM. Eriodictyol showed no pronounced effect on inward rectifying K+ and Ca2+ currents. Furthermore, in KCl depolarized islets, in the presence of diazoxide, insulin secretory ability of eriodictyol was enhanced. IBMX, a phosphodiesterase inhibitor, significantly (P<0.001) enhanced eriodictyol-induced insulin secretion at 16.7mM glucose in comparison to eriodictyol or IBMX alone. The cAMP content after eriodictyol exposure was also increased. Eriodictyol-induced insulin secretion was partially inhibited by adenylate cyclase inhibitor (SQ22536) and completely inhibited by PKA inhibitor (H-89), suggesting that the eriodictyol effect is more on PKA. Molecular docking studies showed the best binding affinities of eriodictyol with PKA. Eriodictyol improved glucose tolerance and enhanced plasma insulin in non-diabetic and diabetic rats. Eriodictyol also lowered blood glucose in diabetic rats upon chronic treatment. Taken together, it can be concluded that eriodictyol, a novel insulin secretagogue, exerts an exclusive glucose-dependent insulinotropic effect through cAMP/PKA pathway.

Trk-fused gene (TFG) regulates pancreatic \u03b2 cell mass and insulin secretory activity

The Trk-fused gene (TFG) is reportedly involved in the process of COPII-mediated vesicle transport and missense mutations in TFG cause several neurodegenerative diseases including hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P). The high coincidence ratio between HMSN-P and diabetes mellitus suggests TFG to have an important role(s) in glucose homeostasis. To examine this possibility, β-cell specific TFG knockout mice (βTFG KO) were generated. Interestingly, βTFG KO displayed marked glucose intolerance with reduced insulin secretion. Immunohistochemical analysis revealed smaller β-cell masses in βTFG KO than in controls, likely attributable to diminished β-cell proliferation. Consistently, β-cell expansion in response to a high-fat, high-sucrose (HFHS) diet was significantly impaired in βTFG KO. Furthermore, glucose-induced insulin secretion was also markedly impaired in islets isolated from βTFG KO. Electron microscopic observation revealed endoplasmic reticulum (ER) dilatation, suggestive of ER stress, and smaller insulin crystal diameters in β-cells of βTFG KO. Microarray gene expression analysis indicated downregulation of NF-E2 related factor 2 (Nrf2) and its downstream genes in TFG depleted islets. Collectively, TFG in pancreatic β-cells plays a vital role in maintaining both the mass and function of β-cells, and its dysfunction increases the tendency to develop glucose intolerance.

Differential effects of age and sex on insulin sensitivity and body composition in adolescent offspring of women with type 1 diabetes: results from the EPICOM study.

The aim of this study was to investigate the influence of age and sex on insulin sensitivity and insulin secretion in the adolescent offspring of women with type 1 diabetes, compared with the background population. This was a prospective nationwide follow-up study (Epigenetic, Genetic and Environmental Effects on Growth, Cognitive Functions and Metabolism in Offspring of Women with Type 1 Diabetes [EPICOM]) in a Danish population. We examined 278 offspring of women with type 1 diabetes from the Danish Diabetes Association Register born during 1993-1999 (index offspring) and 303 control offspring, identified through the Danish Central Office of Civil Registration and matched to the index offspring with respect to date of birth, sex and postal code. The offspring had an overall mean age of 16.7years (range 13.0-20.4years). The main outcomes were age-related changes in fasting OGTT-derived indices for insulin sensitivity (BIGTT-SI0-30-120, Matsuda index, HOMA-IR) and insulin secretion (acute insulin response [BIGTT-AIR0-0-30-120], insulinogenic index, HOMA of insulin secretory function [HOMA-β], disposition index) and physical activity (International Physical Activity Questionnaire). In addition, we determined total body fat (TBF) percentage using dual-energy x-ray absorptiometry. We observed significantly lower insulin sensitivity in index offspring compared with control offspring, increasing with age. The differences were attenuated after adjustment for TBF percentage, but were still significant at 17 and 18years of age. We also observed decreased disposition index and insulin secretion-sensitivity index-2 in index offspring at the same age, but we found no significant differences in other indices of insulin secretion compared with control offspring. With age, TBF percentage became increasingly more divergent between index and control offspring, and was consistently higher among female but not male index offspring. Differences in insulin sensitivity between the offspring of women with type 1 diabetes and control offspring increased with age. This was only partially explained by higher adiposity in the index offspring. ClinicalTrials.gov NCT01559181.

Tocotrienols Stimulate Insulin Secretion of Rat Pancreatic Isolated Islets in a Dynamic Culture.

Tocotrienols (T3) are the naturally occurring vitamin E derivatives that possess antioxidant properties and therapeutic potential in diabetic complications. The bioactivities of the derivatives are determined by the number and arrangement of methyl substitution on the structure. The objective of this study was to determine the effects of T3 derivatives, σ-T3, γ-T3 and α-T3 on insulin secretion of rat pancreatic islets in a dynamic culture. Pancreatic islets isolated from male Wistar rats were treated with T3 for 1 h at 37°C in a microfluidic system with continuous operation that provided a stable cell culture environment. Glucose (2.8 mM and 16.7 mM, as basal and stimulant, respectively) and potassium chloride (KCl) (30 mM) were added to the treatment in calcium free medium. The supernatant was collected for insulin measurements. Short-term exposure (1 h) of σ-T3 to β cells in the stimulant glucose condition significantly potentiated insulin secretion in a dose-dependent manner. γ-T3 and α-T3 also displayed dosedependent effect but were less effective in the activation of insulin secretion. Essentially, KCl, a pancreatic β cell membrane depolarizing agent, added into the treatment further enhanced the insulin secretion of σ-T3, γ-T3 and α-T3 with ED50 values of 504, 511 and 588 µM, respectively. The findings suggest the potential of σ-T3 in regulating glucose-stimulated insulin secretion (GSIS) in response to the intracellular calcium especially in the presence of KCl.

A NEW STAD MODEL TO PREDICT THE DIABETES MELLITUS

Diabetes-mellitus refers to the metabolic disorder that happens due to less insulin secretion action. It is characterized by hyperglycemia. The persistant hyperglycemia of diabetes leads to damage, malfunction and failure of different organs such as kidneys, eyes, nerves, blood vessels and heart. Detection and diagnosis of diabetes at an early stage is the need of the day. Diabetes disease diagnosis and interpretation of the diabetes data is an important classification problem. A variety of data mining techniques are used to discover new patterns of disease and promote the early detection and diagnosis of complex diseases such as diabetes Rule extraction is on among them. The rules are extracted from the dataset. The extracted rules may not only be highly accurate, but also simple and easy to understand. Therefore in this study, The rule extraction algorithm Enhanced STAD model is proposed to achieve highly accurate, concise, and interpretable classification rules for the pima Indian diabetes(PID) dataset, which comprises 768 samples with two classes(diabetes or non-diabetes) and eight attributes. The advanced decision tree algorithm is generated and used for classification. STAD model achieved substantially better accuracy and provided a considerably fewer average number of rules and antecedents. These results suggest that proposed algorithm, is more suitable for medical decision making including the diagnosis of all type of diabetes mellitus.

Isolation and characterization of non-sulfated and sulfated triterpenoid saponins from Fagonia indica

Seven previously undescribed, sulfated triterpenoid glycosides, named nayabin A-G along with a known triterpenoid glycoside were isolated from the whole plant of Fagonia indica. Their structures were elucidated through spectral studies including 1D- (1H and 13C), 2D-NMR spectroscopy (HSQC, HMBC, COSY and NOESY), and mass spectrometry (ESI-MS/MS). β-D-Glucopyranosyl 3β-hydroxy-23-O-β-D-glucopyranosyloxy-taraxast-20-en-28-oate, a known compound exerts glucose-dependent insulin secretory activity, which seems to exhibit a decreased risk of drug-induced hypoglycemia and may offer distinct advantages as anti-diabetic agent.