Deficient Insulin Secretion Research Articles

Citrus flavonoids as a target for the prevention of pancreatic β-cells dysfunction in diabetes.

The number of patients with type 2 diabetes mellitus (T2DM) has rapidly increased, especially in East and Southeast Asia. In these areas, in general, people have especially vulnerable β-cells and insulin secretion deficiency and reduced β-cell mass are the primary cause of T2DM. Therefore, the alleviation of such β-cell dysfunction would provide therapeutic approaches to prevent the development of T2DM. Nobiletin, a polymethoxylated flavonoid found in citrus fruits, has been shown to improve obesity and insulin resistance in T2DM model mice. We focused on β-cells and investigated the effects of nobiletin on insulin secretion and β-cell apoptosis. In β-cell line INS-1, nobiletin increased glucose-induced insulin secretion (GSIS) in a concentration-dependent manner, which was inhibited by an Epac inhibitor. In addition, nobiletin at 10 μM inhibited thapsigargin-induced apoptosis, which was inhibited by a PKA inhibitor. Nobiletin also suppressed thapsigargin-induced increases in cleaved caspase-3 and phosphorylated JNK. Thus, nobiletin is suggested to promote GSIS and prevent ER stress-induced β-cell apoptosis, which are mediated via Epac and PKA-dependent pathways, respectively. In summary, nobiletin is suggested to exhibit insulinotropic and anti-apoptotic effects on β-cells, which are one of the causes of its anti-diabetic effect. Moreover, nobiletin seems to be able to alleviate the development of T2DM by protecting β-cells from apoptosis.

Selectively Bred Diabetes Models: GK Rats, NSY Mice, and ON Mice.

The polygenic background of selectively bred diabetes models mimics the etiology of type 2 diabetes. So far, three different rodent models (Goto-Kakizaki rats, Nagoya-Shibata-Yasuda mice, and Oikawa-Nagao mice) have been established in the diabetes research field by continuous selective breeding for glucose tolerance from outbred rodent stocks. The origin of hyperglycemia in these rodents is mainly insulin secretion deficiency from the pancreatic β-cells and mild insulin resistance in insulin target organs. In this chapter, we summarize backgrounds and phenotypes of these rodent models to highlight their importance in diabetes research. Then, we introduce experimental methodologies to evaluate β-cell exocytosis as a putative common defect observed in these rodent models.

Antidiabetic Effects and Mechanisms of Rosemary (Rosmarinus officinalis L.) and its Phenolic Components.

Diabetes mellitus is a chronic endocrine disease result from absolute or relative insulin secretion deficiency, insulin resistance, or both, and has become a major and growing public healthy menace worldwide. Currently, clinical antidiabetic drugs still have some limitations in efficacy and safety such as gastrointestinal side effects, hypoglycemia, or weight gain. Rosmarinus officinalis is an aromatic evergreen shrub used as a food additive and medicine, which has been extensively used to treat hyperglycemia, atherosclerosis, hypertension, and diabetic wounds. A great deal of pharmacological research showed that rosemary extract and its phenolic constituents, especially carnosic acid, rosmarinic acid, and carnosol, could significantly improve diabetes mellitus by regulating glucose metabolism, lipid metabolism, anti-inflammation, and anti-oxidation, exhibiting extremely high research value. Therefore, this review summarizes the pharmacological effects and underlying mechanisms of rosemary extract and its primary phenolic constituents on diabetes and relative complications both in vitro and in vivo studies from 2000 to 2020, to provide some scientific evidence and research ideas for its clinical application.

Patch Solid Lipid Nanoparticles (SLN) Mengandung Ekstrak Bekatul (Oryza Sativa L.) untuk Pengobatan Diabetes Melitus Tipe 2

a atau sekresi insulin pankreas yang tidak bekerja dengan baik (resistensi insulin) dimana menjadi salah satu prioritas penyakit tidak menular (noncommunicable diseases/NCDs). Dari kasus diabetes yang ada, 90% diantaranya merupakan diabetes melitus tipe 2 (IDF, 2017). Diabetes tipe 2 atau disebut dengan diabetes non-dependen-insulin ini terjadi karena resistensi jaringan terhadap efek insulin dan defisiensi relatif sekresi insulin (WHO, 2016).Diabetes Melitus Tipe 2 lebih sering didiagnosis pada usia yang lebih rendah dan indeks massa tubuh pada pria dibandingkan wanita. Berbagai faktor risiko diabetes adalah usia, aktivitas fisik, indeks massa tubuh (IMT), tekanan darah, stres, gaya hidup, adanya riwayat keluarga, kolesterol HDL, trigliserida, DM kehamilan, riwayat ketidaknormalan glukosa dan kelainan lainnya. Selain itu, faktor resiko yang berpengaruh adalah kebiasaan merokok dan minum minuman beralkohol (Isnaini, 2018). Berdasarkan data Riskesdas pada tahun 2013, prevalensi perokok laki-laki sebanyak 66% dimana sekitar 10 kali lebih tinggi dibandingkan perempuan yaitu sebanyak 6,7% (Pusat Data dan informasi Kementerian Kesehatan RI, 2013).Penderita diabetes melitus tipe 2, selain memerlukan terapi non-farmakologis seperti mengatur pola makan, berolahraga, tidak merokok dan tidak minum minuman beralkohol juga memerlukan terapi farmakologis yang dapat dilakukan dengan menyuntikkan insulin dan/atau meminum obat antidiabetik oral (Neal, 2012). Namun penggunaan terapi pengobatan dengan insulin memiliki masalah pada pasien yang takut dengan jarum suntik, selain itu pengobatan dengan antidiabetik oral juga memiliki beberapa masalah yaitu adanya efek samping seperti penurunan berat badan, hipoglikemia, gangguan sistem pencernaan, dan lain-lain. Biaya pengobatan diabetes sendiri cukup mahal karena pengobatannya dalam jangka panjang dan bahkan bisa seumur hidup. Biaya yang diperlukan untuk memberi terapi pada pasien yang telah terdiagnosis diabetes di seluruh dunia pada 2011 hingga 2030 sebanyak 1,7 triliun US$ (WHO, 2016). Mempertimbangkan biaya pengobatan diabetes yang cukup tinggi dan efek samping yang ditimbulkan oleh obat-obat antidiabetes diperlukan suatu terapi alternatif dengan harga yang relatif murah dan memiliki potensi yang kuat serta memiliki efek samping yang minimal. Hal tersebut dapat dilakukan dengan menggunakan limbah namun berkhasiat dalam terapi pengobatan diabetes melitus, diantaranya adalah bekatul (Sivamaruthi, Kesika and Chaiyasut, 2018).

Anti-Diabetic Activity of Egyptian Celery Apigenin

Diabetes is a metabolic disorder that occurs due to a deficiency in insulin secretion, action or both of them. Apigenin is a potent antioxidant, found mainly in celery. Therefore, this study aimed to display the biological activity of apigenin and it is a role in lowering blood glucose levels. Apigenin has been extracted from celery and administrated daily to streptozotocin-diabetic rats for six weeks. Apigenin significantly minimizes blood glucose level, the activities of á-amylase, lipid profile and malondialdehyde in serum. On the other hand, liver glycogen has been elevated in diabetic rats that treated with apigenin. The histopathological and immunohistochemical results confirmed that apigenin can decrease degenerative changes in the pancreatic â-cells. So, this study, depicts that apigenin considers a hypoglycemic agent with the potency to normalize odd in the biochemical parameter of diabetes and keep the normal architecture of the islet cells of the pancreas.

Ameliorative potentials of aqueous extracts of leaf and stem of Ipomoea involucrata on selected biochemicals in experimental diabetic rats

Background: Diabetes mellitus is a chronic metabolic disorder characterized by derangements in carbohydrate, protein and lipid metabolisms, due to deficiency in insulin secretion and action. This research evaluates the ameliorative potentials of aqueous extracts of leaves and stem of Ipomoea involucorata on selected biochemicals in experimental diabetic rats.Methods: Diabetes mellitus was induced by single intraperitoneal injection of 150 mg/kg body weight of alloxan and the animals were orally administered with gilanil (4 mg/kg) for positive control, 100, 200 and 300 mg/kg bw aqueous extract of leaves (groups 4-6) and stem (groups 7-9) of Ipomoea involucrata once daily for 21 days. Biochemical parameters were analysed using standard methods.Results: The median lethal dose was established at 648 mg/kg (leaves) and 547 mg/kg (stem). The negative group (untreated) showed significant increase in glucose concentration compared to the other groups. After 2 to 3 weeks there was significant (p<0.05) decrease in glucose concentration of the extract and glibenclamide (positive group) treated groups when compared with the negative group. Diabetes control rats showed significant (p<0.05) high serum lipid profile (except for high density lipoprotein), liver enzymes/ indices and renal indices when compared with non-diabetic control rats. However, these alternations were reversed with the positive group and the groups treated with aqueous extracts of both samples. The differences observed in the electrolytes were not significant in all groups.Conclusions: The results suggest that aqueous extract of leaves and stem of I. involucrata is considerably safe and a potential therapy for management of complications associated with diabetes mellitus.

Approach to creating early diabetic peripheral neuropathy rat model

To create the early diabetic peripheral neuropathy (DPN) rat model. After one-week adaption, 26 male Sprague-Dawley (SD) rats were divided into two groups, the control group (n=6) and the model group (n=20). High-sucrose/high-fat diet (D12451, 35% of energy from carbohydrate, 45% of energy from fat) was given to the model group for six weeks to induce insulin resistance, meanwhile normal diet was given to the control group. Afterwards, streptozocin (STZ) buffer solution (35 mg/kg bodyweight) was injected into abdomen of the model group to induce specific pancreatic injury, meanwhile an equal amount of buffer solution was given to the control group. Then 48 h later, type 2 diabetes mellitus (T2DM) was supposed to be successfully induced according to the random blood glucose more than 16.7 mmol/L in the model group. Then the basic features of the T2DM rats were evaluated, including body weight, fasting blood glucose (FBG), glucose tolerance (oral glucose tolerance test, OGTT), and insulin tolerance (intraperitoneal insulin tolerance test, IPITT). Subsequently, withdrawal thermal latency (WTL) was measured regularly to determine when the early DPN occurred. Once confirmed, sciatic nerve conduction velocity (NCV) of all the rats was conducted. The T2DM rats were successfully induced in the model group through high-sucrose/high-fat diet for six weeks along with STZ intraperitoneal injection (35 mg/kg bodyweight). When compared to the control group, the T2DM rats had higher FBG (P<0.001), and the glucose tolerance and insulin tolerance were both damaged (P<0.001 in OGTT, P=0.002 in IPITT). It was on the 17th day when the T2DM rats became much more sensitive to heat stimulus compared to the control group (P=0.004). Meanwhile, the sciatic NCV was conducted. There was no significant difference between the early DPN group and the control group (P=0.196). High-sucrose/high-fat diet for six weeks along with STZ intraperitoneal injection (35 mg/kg bodyweight) could successfully induce T2DM rat model, manifested by a certain extent of insulin resistance and deficiency of insulin secretion. It was about 17 days later when the early DPN emerged. In the early DPN, small fiber neuropathy came out earlier than large fiber neuropathy.

Estimation of Serum Homocysteine and Vitamin B12 in Type 2 Diabetes Mellitus Patients

Background: Diabetes mellitus is a common metabolic disorder characterized by absolute or relative deficiencies in insulin secretion and/or insulin action associated with chronic hyperglycemia and disturbances of carbohydrate, lipid and protein metabolism. Homocysteine (Hcy) is a risk factor strongly linked to cardiovascular complications in Type 2 Diabetes mellitus (T2DM). Hcy requires 5-methyltetrahydrofolate as methyl donor and vitamin B12 as a co-factor. So, Vitamin B12 deficiency will lead to hyperhomocysteinemia. Biochemical and clinical vitamin B12 deficiency has been demonstrated to be highly prevalent among patients with type 1 and type 2 diabetes mellitus.&#x0D; Aims: To assess the serum homocysteine and vitamin B12 levels in type 2 Diabetes mellitus patients.&#x0D; Methodology: The present case control study was conducted at Dhiraj hospital, Piparia, Vadodara, Gujarat, India in which 80 subjects were enrolled, out of which 40 were cases of type 2 diabetes mellitus patients and 40 were controls. The age group for the study was 35 to 70 years. Blood samples were drawn to measure RBS, HbA1c, serum homocysteine and vitamin B12. Interpretation of data was done using Medcalc software.&#x0D; Results: The mean levels of serum homocysteine was higher in T2DM patients than normal healthy individuals, difference between them was statistically highly significant (p&lt;0.0001). The mean levels of vitamin B12 was lower in T2DM patients than normal healthy individuals, difference between them was statistically highly significant (p&lt;0.0001). There is no correlation found between Homocysteine, vitamin B12 &amp; HbA1c.&#x0D; Conclusion: A significant increase in serum Hcy level was observed in T2DM patients in our study. Raised serum Homocysteine is considered as an early marker of B12 deficiency. Hyperhomocysteinemia will lead to cardiovascular complications. Therefore, the hyperhomocysteinemia could serve as another important marker of poor diabetic control and developing complications.

Thyroid profile in type 2 diabetes mellitus

Background: Diabetes mellitus is an endocrine disorder which involves multiple organ systems and leads to significant morbidity and mortality. Diabetes mellitus has been defined as “A metabolic syndrome characterized by chronic hyperglycemia and disturbance of carbohydrate, fat and protein metabolism associated with absolute or relative deficiency in insulin secretion and or insulin action”. Thyroid diseases are also a common endocrinopathy seen in the adult population. Thyroid hormones are intimately involved in cellular metabolism. The present work is a modest attempt to study the prevalence of thyroid disorders in patients with type 2 diabetes mellitus.Methods: The study was carried out in total 108 diabetic patients without known thyroid disorder admitted in various Medical wards of R.N.T. Medical college and attached group of hospitals, Udaipur. It was a cross Sectional study done over a period of 10 months. Results: In the present study, 13% of patients with type 2 diabetes mellitus had abnormal thyroid profile. Out of which the most common presentation was sub clinical hypothyroidism found in 9.25% followed by1.9% had overt hypothyroidism and 1.9% had sub clinical hyperthyroidism. In persons with abnormal thyroid profile 85.7% were females and 14.3% were males which was statistically significant.Conclusions: Prevalence of thyroid dysfunction is common among T2DM patients and is higher in females than in males. There is no significant correlation between thyroid dysfunction and age, diabetes control, family history, type of treatment and HbA1c level in diabetic patients.

Side-Effects of Diabetic Individuals with Bacterial-Infection of Non-Foot-Wounds Affecting Individuals-Community-Health at High-Altitude Area, “Taif ”, KSA

Diabetic is a clinical syndrome associated with deficiency of insulin secretion or action. It is considered one of the largest emerging threats to health in the 21st century...

PDB102 TARGETED LITERATURE REVIEW INTO METHODS OF DETERMINING PATIENTS' PREFERENCE FOR TREATMENT TYPE IN DIABETES

Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition characterised by deficient secretion of insulin along with insulin resistance, and consequent poor glycaemic control. The variety of possible therapies available for T2DM requires payers and prescribers to consider the additional effects and requirements of treatment regimens, beyond simply their impact on glycaemic control. As side effects and treatment complexity are known to affect adherence, it is therefore important to consider patient preferences for all effects and requirements of therapy. We completed a targeted literature review across multiple databases to identify published literature detailing methods of determining patient preference and willingness-to-pay for treatments for T2DM. The literature review identified 32 publications of relevance to the study objectives. The majority of these studies (n=29) used a discrete choice experiment (DCE) study design and most studies were completed in the US (n=13). Attributes of treatment preference presented to patients ranged across the studies and included: hypoglycaemic events, cardiovascular health, weight changes, mode of administration and characteristics of device. Patient preference for oral versus injectable therapy was most commonly studied (n=13), followed by injection only (n=8) and oral only (n=5). The most common attributes from participants were: age (n=27), gender (n=27), education (n=20), duration with diabetes (n=19) and HbA1c level (n=19). Both glucose control (n=5) and number of hypoglycaemia events (n=5) were the second most important attributes to a patient. All studies measuring patient preference for oral versus injectable therapy showed oral therapy was preferred. In general, identified publications were consistent in the approaches taken to develop surveys, collect and analyse preference data. Recommendations for future research from this review include: employing a forced-choice DCE methodology, using approximately 6 attributes in choice sets, attributes should be selected following consultation with experienced persons.

HEALTH-RELATED QUALITY OF LIFE (HR-QOL) IN DIABETIC PATIENTS OF TYPE 2 IN GAZA, PALESTINE

Introduction: Diabetes mellitus is a multifactorial disease caused by deficiency in insulin secretion, insulin action, or both. Poor quality of life contributes to decreased personal care, which in turn contributes to worsening glycemia control, enhanced risk of diabetic complications. This study aimed to determine the health-related quality of life (HRQOL) for diabetics as compared to gender-age matched control living in southern Gaza, Palestine. Methods: This study was a case-control. About 100 DM patients and age-sex matched 100 controls were randomly selected from the department of internal medicine at the Nasser Medical Complex in Khanyunis Governorate and the community. The World Health Organization Quality of Life Questionnaire – short version (WHOQOL-BREF) was used to evaluate the quality of life among the study population. Results: Those with diabetics, the HRQOL was significantly lesser than for controls in all domains with the largest differences in the environmental domains (difference of 5 points) and tinier differences in physical health, psychological health &amp; social relationships (2, 3 and 3 points difference) (&lt;0.001 for all). Low ratings in the field of social relations in both groups with tiny differences between them have been registered (3 points). Furthermore, there were no differences in mean of scores for all domains according to gender. Conclusion: The study population's total HRQOL (diabetics and controls) was poor. Health program must be developed to encourage improve dietary habits, healthier lifestyle, promote exercise, discourage smoking, avoid complications of diabetes and appropriately handle chronic diseases.

Dracorhodin perchlorate protects pancreatic β-cells against glucotoxicity- or lipotoxicity-induced dysfunction and apoptosis invitro and invivo.

Glucotoxicity or lipotoxicityleads to hyperglycemia and insulin secretion deficiency, which are important causes for the onset of type 2 diabetes mellitus (T2DM). Thus, the restoration of β-cell function is a long-sought goal in diabetes research. Previous studies have implicated pancreatic and duodenal homeobox 1 gene (Pdx1) in β-cell function and insulin secretion. In this study, we established a Pdx1 promoter-dependent luciferase system and identified the natural compound dracorhodin perchlorate (DP) as an effective promotor of Pdx1 expression. We further demonstrated that DP could significantly inhibit β-cell apoptosis induced by 33mm glucose or 200 μm palmitate by interfering with endoplasmic reticulum stress and mitochondrial pathways and enhance insulin secretion as well. These effects were associated with enhanced activities of Erk1/2, which in turn promoted Pdx1 expression and increased the ratio of Bcl2/Bax, since inhibition of the Erk1/2 pathway abolished the DP-induced expression of Pdx1 and suppression of apoptosis. In addition, our invivo results in diabetic mice indicated that DP treatment lowered blood glucose, raised insulin levels, enhanced Pdx1 expression and increased islet size and number in the pancreas of diabetic mice. Our findings suggest that Pdx1 is a potential target molecule of DP in the treatment of T2DM via the inhibition ofglucotoxicity- or lipotoxicity- induced β-cell apoptosis and the attenuation of insulin secretion dysfunction.

Investigation of goodness of model data fit using PLSR and PCR regression models to determine informative wavelength band in NIR region for non-invasive blood glucose prediction

Diabetes mellitus is a metabolic disorder characterized by the deficiency in insulin secretion or insulin action on target tissues. Diabetes being diagnosed, requires frequent monitoring. Current measurement techniques are invasive in nature, which is painful. Non-invasive measurement methods for the prediction of blood glucose is a big challenge. Hence this paper focuses on a comparative study to analyze the performance of the two regression models: partial least square regression (PLSR) and principal component regression (PCR) models to arrive at the best regression model for the prediction of blood glucose non-invasively based on NIR diffuse reflectance spectroscopy. The regression model developed involves spectral data collected from 32 subjects from a diabetic center using diffuse reflectance spectrometer (DRS). The spectroscopic data were acquired from the subjects both invasively using clinical method and non-invasively using DRS setup in the NIR spectral range whose wavelength ranges from 750 to 1040 nm. Multivariate analysis using PLSR is found to be a better regression model in terms of the fitted response and estimated mean square prediction error. It is observed that the mean square error value is 0.04 mg/dl for the tenth component in the PLSR model. The developed regression model also proves to be a useful tool in identifying the informative wavelength bands for blood glucose measurement.

1077-P: Treatment of Post-pancreatectomy Diabetes in Individuals with Congenital Hyperinsulinism Using a Bihormonal Bionic Pancreas

Congenital Hyperinsulinism (HI) is a disorder of beta-cell function that results in severe hypoglycemia. Near-total pancreatectomy (Ppx) is necessary for intractable hypoglycemia in the most severe cases, which results in diabetes later in life. The evolution of diabetes after Ppx is characterized by marked hypo- and hyper-glycemia due to residual dysregulated insulin secretion and glucagon deficiency. We aim to evaluate the safety and efficacy of a bihormonal bionic pancreas (BHBP) in individuals with HI and post-Ppx diabetes. Autonomously adaptive dosing algorithms in the BHBP use data from an integrated continuous glucose monitor (CGM) to control subcutaneous delivery of insulin and glucagon. Our hypothesis is that the BHBP will result in improved glycemic control compared to conventional insulin pump (CIP) therapy. This is an open-label, random-order, crossover, pilot study. Subjects with HI and post-Ppx diabetes are randomly assigned to BHBP therapy or CIP therapy during a 4-day inpatient stay, followed by the opposite intervention at least 1 week later. The BHBP was initialized with only the subject’s body weight. The coprimary outcomes are mean glucose and time with CGM glucose &amp;lt; 60 mg/dL analyzed over days 2-4. Seven subjects age 7-25 years (4 F) with mean A1C of 7.5% (SD 0.57) have completed the study to date. Mean CGM glucose was 148 mg/dL (SD 14) during the BHBP period vs. 156 mg/dL (SD 28) during the CIP period. All subjects had mean glucose during their BHBP period at or below 169 mg/dL (corresponding to A1C of 7.5%), whereas only 57% of subjects met this goal during their CIP period. Mean time with CGM glucose &amp;lt; 60 mg/dL was 0.07% (SD 0.60%) during the BHBP period vs. 1.71% (SD 3.48) during the CIP period. The BHBP was well tolerated. Relative to CIP therapy, the BHBP was able to produce, with greater ease of use, comparable, if not superior, results in terms of mean glucose and reduced frequency of hypoglycemia in individuals with HI and post-Ppx diabetes. Disclosure A. Rayannavar: None. L.M. Mitteer: None. K. Lord: None. C.P. Hawkes: None. C.A. Balliro: None. F. El-Khatib: Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. E. Damiano: Advisory Panel; Self; Novo Nordisk A/S. Board Member; Self; Beta Bionics. Employee; Self; Beta Bionics. Stock/Shareholder; Self; Beta Bionics. Stock/Shareholder; Spouse/Partner; Beta Bionics. Other Relationship; Self; Ascensia Diabetes Care, Senseonics. S.J. Russell: Advisory Panel; Self; Companion Medical, Unomedical a/s. Consultant; Self; Flexion Therapeutics. Research Support; Self; Beta Bionics, MITRE Corporation, Novo Nordisk A/S, Zealand Pharma A/S. Other Relationship; Self; ADOCIA, Ascensia Diabetes Care, Ascensia Diabetes Care, Lilly Diabetes, Roche Diabetes Care, Senseonics. D. De Leon: Consultant; Self; Crinetics, Novartis Pharmaceuticals Corporation, ProSciento, Soleno Therapeutics, Zealand Pharma A/S. Employee; Spouse/Partner; Merck &amp; Co., Inc. Research Support; Self; Crinetics, Dexcom, Inc., Zealand Pharma A/S. Stock/Shareholder; Self; Merck &amp; Co., Inc. Funding Zealand Pharma A/S; Dexcom, Inc.; University of Pennsylvania; Children's Hospital of Philadelphia Women's Committee; National Institutes of Health (T32DK06368-14 to A.R.); Pediatric Endocrine Society

346-LB: The Role of STAT3 Signaling toward a-to-ß Reprogramming within the Adult Pancreas

As diabetes mellitus results from the absolute or relative deficiency of insulin secretion from pancreatic β cells, the generation of surrogate β cells has attracted a lot of attention for the cure of diabetes. To date, insulin-producing cells have been generated from differentiated cell types in the pancreas, such as acinar cells and α cells, by inducing the exogenous expression of pancreas-specific transcription factors. However, it still remains unclear as to how surrogate β cells can be efficiently generated toward establishing future regenerative therapies for diabetes. STAT3 has been demonstrated to play a role in maintaining cellular identities in the pancreas, and we have reported that the activation of STAT3 signaling is required for acinar-to-ductal transition (Miyatsuka et al. Genes Dev. 2006), whereas the suppression of STAT3 signaling efficiently promotes acinar-to-β reprogramming (Miura M. et al. EBioMedicine. 2018). Therefore, we hypothesized that regulating STAT3 signaling may control the efficiency of α-to-β reprogramming. To address this, we generated transgenic mice that exogenously express Pdx1, Mafa and Ngn3 specifically in α cells, and deleted Stat3 in a tamoxifen inducible manner (Stat3KO; Gcg-CreERT2; Pdx1;Ngn3;Mafa mice: αStat3KO;PNM mice). Immunofluorescent imaging demonstrated that Stat3 deletion significantly increased the number of α-cell-derived insulin-producing cells in αStat3KO;PNM mice, compared with control mice (28.2±2.7 vs. 8.6±3.1%, p&amp;lt;0.05). Notably, 61.2±8.8% of α-cell-derived insulin-producing cells were negative for glucagon in αStat3KO;PNM mice, which was higher compared with controls (36.4±18.0 %). These results suggest that the suppression of STAT3 signaling efficiently promotes α-to-β reprogramming as well as acinar-to-β reprogramming in mice. Disclosure Y. Wakabayashi: None. T. Miyatsuka: None. L. Suzuki: None. M. Himuro: None. T. Katahira: None. M. Miura: None. H. Watada: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Kissei Pharmaceutical Co., Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Pfizer Inc., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited, Teijin Pharma Limited. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Sanofi, Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Kowa Pharmaceutical Europe Co. Ltd., Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Ono Pharmaceutical Co., Ltd., Sanwa Chemical Industry Co. Ltd., Takeda Pharmaceutical Company Limited.

Aktivitas Antidiabetika Kombinasi Fraksi Etil Asetat Buah Pare (Momordica charantia L.) dan Rimpang

Diabetes Mellitus type 2 can be caused by the resistance of tissue towards insulin accompanied by relative deficiency in insulin secretion. Insulin resistance factor can result from obesity. This research aims to investigate anti- diabetic activity of the compound of FEA of curcuma (Curcuma domestica Val) and bitter melon (Momordica charantia L.). Subjects of this research were 40 albino Wistar rats (Rattus norvegicus) aged 5-8 weeks. The rats were randomly grouped into 8 experimental groups in which each group consisted of'5 rats. The tested animals were divided into 6 groups, KG) metformin 45 mg/Kg BB, P1: FEA curcuma 10 mg/ 200g BB, P2: FEA bitter melon 04 mg/ 200g BB, P3: Compound of FEA curcuma : FEA bitter melon 5 : 0,8 mg/200g BB, P4: Compound of FEA curcuma : FEA bitter melon 10 : 04 mg/200g BB, and P5: Compound of FEA curcuma : FEA bitter melon (20 : 02mg9/200g BB). The animals were inducted with insulin resistance with the giving of HFD-fructose. Result showed that the compound of FEA of curcuma (Curcuma domestica Val) and FEA of bitter melon (Momordica charantia L.) had the activity of lowering blood glucose level: the best anti-diabetic activity was identified in the compound of FEA of curcuma and FEA of bitter melon at the dose of 20: 0,2m9g/200g BB in the rats with HFD- fructose. Normal 0 false false false IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin-top:0cm; mso-para-margin-right:0cm; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0cm; mso-pagination:widow-orphan; font-size:11.0pt; font-family:Cambria,serif; mso-ascii-font-family:Cambria; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:Times New Roman; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Cambria; mso-hansi-theme-font:minor-latin;} Diabetes Mellitus type 2 can be caused by the resistance of tissue towards insulin accompanied by relative deficiency in insulin secretion. Insulin resistance factor can result from obesity. This research aims to investigate anti- diabetic activity of the compound of FEA of curcuma (Curcuma domestica Val) and bitter melon (Momordica charantia L.). Subjects of this research were 40 albino Wistar rats (Rattus norvegicus) aged 5-8 weeks. The rats were randomly grouped into 8 experimental groups in which each group consisted of'5 rats. The tested animals were divided into 6 groups, KG) metformin 45 mg/Kg BB, P1: FEA curcuma 10 mg/ 200g BB, P2: FEA bitter melon 04 mg/ 200g BB, P3: Compound of FEA curcuma : FEA bitter melon 5 : 0,8 mg/200g BB, P4: Compound of FEA curcuma : FEA bitter melon 10 : 04 mg/200g BB, and P5: Compound of FEA curcuma : FEA bitter melon (20 : 02mg9/200g BB). The animals were inducted with insulin resistance with the giving of HFD-fructose. Result showed that the compound of FEA of curcuma (Curcuma domestica Val) and FEA of bitter melon (Momordica charantia L.) had the activity of lowering blood glucose level: the best anti-diabetic activity was identified in the compound of FEA of curcuma and FEA of bitter melon at the dose of 20: 0,2m9g/200g BB in the rats with HFD- fructose. Diabetes Mellitus type 2 can be caused by the resistance of tissue towards insulin accompanied by relative deficiency in insulin secretion. Insulin resistance factor can result from obesity. This research aims to investigate anti- diabetic activity of the compound of FEA of curcuma (Curcuma domestica Val) and bitter melon (Momordica charantia L.). Subjects of this research were 40 albino Wistar rats (Rattus norvegicus) aged 5-8 weeks. The rats were randomly grouped into 8 experimental groups in which each group consisted of'5 rats. The tested animals were divided into 6 groups, KG) metformin 45 mg/Kg BB, P1: FEA curcuma 10 mg/ 200g BB, P2: FEA bitter melon 04 mg/ 200g BB, P3: Compound of FEA curcuma : FEA bitter melon 5 : 0,8 mg/200g BB, P4: Compound of FEA curcuma : FEA bitter melon 10 : 04 mg/200g BB, and P5: Compound of FEA curcuma : FEA bitter melon (20 : 02mg9/200g BB). The animals were inducted with insulin resistance with the giving of HFD-fructose. Result showed that the compound of FEA of curcuma (Curcuma domestica Val) and FEA of bitter melon (Momordica charantia L.) had the activity of lowering blood glucose level: the best anti-diabetic activity was identified in the compound of FEA of curcuma and FEA of bitter melon at the dose of 20: 0,2m9g/200g BB in the rats with HFD- fructose. 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Insulin Resistance in Adults with Type 1 Diabetes is Associated with Lower Vitamin D Serum Concentration.

Type 1 diabetes mellitus (T1DM) is a disease characterized by an absolute deficiency of endogenous insulin secretion. Insulin resistance (IR) may develop among patients with T1DM. Vitamin D deficiency was reported to be a risk factor in the development of IR. The aim of the study was to assess the relationship between serum concentrations of 25-hydroxyvitamin D (25(OH)D) and IR among patients with T1DM. The test group consisted of 110 adult patients [males=65 (59%)] with T1DM. Participants were recruited in Poland between 1st October and 30th April in 2015/2016 and 2016/2017. VD serum level was assessed by ELISA array. IR was assessed by estimated Glucose Disposal Rate (eGDR). In the study group 21 (19%) patients were recognized as IR according to eGDR cut-offs (<7.5 mg/kg/min), 52 (47.3%) patients had VD deficiency (25(OH)D<20 ng/ml), 16 (14.5%) patients had 25(OH)D<10 ng/ml. Only 6 (5%) participants reported VD supplementation. Patients with IR, according to eGDR cut-off revealed significantly lower 25(OH)D serum level 15.7 (9.2-28.4) vs. 22.1 (13.0-38.4) ng/ml; p=0.04 as compared to patients without IR. R Spearman analysis found a positive relationship between VD and eGDR (Rs=0.27; p<0.01). Logistic regression analysis revealed significant relationship between the presence of IR and VD serum level/presence of 25(OH)D serum level below 10 ng/ml, both models adjusted to sex, age, BMI, LDL and triglycerides, accordingly (OR=0.95, CI: 0.90-0.99; p=0.04) and (OR=4.19, CI: 1.04-16.93; p=0.04). The serum concentration of Vitamin D is negatively associated with insulin resistance in patients with T1DM and may have clinical implications.

Effects of Nicorandil and Chronic Physical Exercise on Glycemia in Diabetic Rats Induced by Streptozotocin

Diabetes is a chronic metabolic disease characterized by persistent hyperglycemia caused by a decrease or deficiency of insulin secretion and/or peripheral insulin resistance. Regular physical exercise could improves glucose metabolism and insulin sensitivity, which is essential for preventing diabetic complications. Moreover, there is evidence that the opening of ATP sensitive potassium (KATP) channels contributes to cytoprotective effects under metabolic stress, therefore KATP channels could be a therapeutic target in this disease. Thus, the purpose of this study was to assess the impact of the potential effects of nicorandil (KATP channel opener) after a chronic exercise training program on levels glicemic in diabetic rats.Male Wistar rats (23–25 days old) were randomly divided into six groups, among them: sedentary control, trained control, sedentary diabetic, trained diabetic, sedentary diabetic plus nicorandil, trained diabetic plus nicorandil. Diabetes was induced by a single streptozotocin injection (100 mg/kg body weight), animals with fasting blood glucose levels ≥ 250 mg/dL were considered as diabetic. Training comprised 8 weeks of treadmill running (30 minutes daily, 5 days/week); at week 4, nicorandil (3 mg/kg) was administered for to 4 weeks. Fasting blood glucose (FBG) level was recorded every week for 8 consecutive weeks. At the end of experimental protocol, insulin tolerance test (ITT) was evaluated in all groups, rats received a application of insulin (0.75UI/kg body weight), with blood samples drawn after 0, 30, 60, 90 and 120 min postinjection. Blood glucose response to ITT was calculated as area under the curve (AUC‐ITT) of the blood glucose excursion along 120 minutes after intra‐peritoneal insulin injection and correlated with the corresponding fasting values according to the trapezoidal method.Treatment with nicorandil and the chronic exercise exerted remarkable effects on hyperglycemic status in diabetic rats by decreases FBG levels (47.51± 10.2 %) and inducing significant increases in the insulin sensitivity (P&lt; 0.05) compared with sedentary diabetic rats and trained diabetic rats. Our results suggest than opening KATP channels by nicorandil mediates potential benefits the chronic physical exercise on glycemic in diabetes.Support or Funding InformationWe thank Universidad de Guanajuato, Campus León. We acknowledge the financing PRODEP (Programa para el Desarrollo Profesional Docente en Educación Superior, ESD (511‐6/18‐8876).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Comparative study of hypoglycemic activity of Morus alba with oral glibenclamide in streptozotocin induced diabetic rats

Background: Diabetes is a chronic metabolic disorder that continues to present a major worldwide health problem, characterized by absolute or relative deficiencies in insulin secretion and/or insulin action associated with chronic hyperglycaemia and disturbances of carbohydrate, lipid, and protein metabolism. It is fast growing disease, gains the status of a potential epidemic in India with prevalence of more than 62 million diabetic individuals currently diagnosed with the diabetes.Methods: The study was conducted at Department of Pharmacology, Kurnool Medical College, Kurnool for a period of 1 year from January 2017 to December 2018. Animals used were albino rats, of Wistar strain, weighing between 150-200gm of either sex. The animals were divided into six groups as: control group (I); pathogenic control group (II) injected intravenously (i.v.) with single dose of STZ (60mg/kg); Morus alba stem bark extract (group-III; 200mg/kg), and group-IV (400mg/kg); group-V animals treated with glibenclamide (5mg/kg, p.o.) following STZ treatment; group-VI, animals treated with bark extract per se (400 mg/kg).Results: The results of this study showed a significant decrease blood glucose level, glycosylated heamoglobin level, and reduction in glutathione and insulin level after STZ administration. These parameters were significantly (p&lt;0.05) reversed by extracts dose dependently.Conclusions: Thus, authors conclude that M. alba stem bark extracts produced significant antidiabetic and antioxidant effect which might be due to the presence of bioactive components such as phenolic and flavonoid content in the extract. The study warrants the need for further evaluated in certain other models of diabetes.