scholarly journals Sam68 promotes hepatic gluconeogenesis via CRTC2

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Aijun Qiao ◽  
Junlan Zhou ◽  
Shiyue Xu ◽  
Wenxia Ma ◽  
Chan Boriboun ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Therapeutic Target ◽  
Rna Binding ◽  
Adaptor Protein ◽  
Diabetic Mouse ◽  
Mrna Levels ◽  
Hepatic Gluconeogenesis ◽  
Kinase Substrate ◽  
Glucose Levels ◽  
Patients With Diabetes

AbstractHepatic gluconeogenesis is essential for glucose homeostasis and also a therapeutic target for type 2 diabetes, but its mechanism is incompletely understood. Here, we report that Sam68, an RNA-binding adaptor protein and Src kinase substrate, is a novel regulator of hepatic gluconeogenesis. Both global and hepatic deletions of Sam68 significantly reduce blood glucose levels and the glucagon-induced expression of gluconeogenic genes. Protein, but not mRNA, levels of CRTC2, a crucial transcriptional regulator of gluconeogenesis, are >50% lower in Sam68-deficient hepatocytes than in wild-type hepatocytes. Sam68 interacts with CRTC2 and reduces CRTC2 ubiquitination. However, truncated mutants of Sam68 that lack the C- (Sam68ΔC) or N-terminal (Sam68ΔN) domains fails to bind CRTC2 or to stabilize CRTC2 protein, respectively, and transgenic Sam68ΔN mice recapitulate the blood-glucose and gluconeogenesis profile of Sam68-deficient mice. Hepatic Sam68 expression is also upregulated in patients with diabetes and in two diabetic mouse models, while hepatocyte-specific Sam68 deficiencies alleviate diabetic hyperglycemia and improves insulin sensitivity in mice. Thus, our results identify a role for Sam68 in hepatic gluconeogenesis, and Sam68 may represent a therapeutic target for diabetes.

scholarly journals Feedback regulation of hepatic gluconeogenesis through modulation of SHP/Nr0b2 gene expression by Sirt1 and FoxO1

2011 ◽  
Vol 300 (2) ◽  
pp. E312-E320 ◽  
Author(s):  
Dan Wei ◽  
Rongya Tao ◽  
Yao Zhang ◽  
Morris F. White ◽  
X. Charlie Dong
Keyword(s):  
Gene Expression ◽  
Blood Glucose ◽  
Catalytic Domain ◽  
Wild Type Mouse ◽  
Diabetic Mouse ◽  
Luciferase Reporter ◽  
Wild Type ◽  
Hepatic Gluconeogenesis ◽  
Glucose Levels ◽  
Blood Glucose Levels

Protein deacetylase Sirt1 has been implicated in the regulation of hepatic gluconeogenesis; however, the mechanisms are not fully understood. To further elucidate how Sirt1 regulates gluconeogenesis, we took a loss-of-function approach by deleting the coding DNA sequence for the catalytic domain of the Sirt1 gene in the liver of a wild-type mouse (LKOSirt1) or a genetic diabetic mouse in which hepatic insulin receptor substrates 1 and 2 are deleted (DKOIrs1/2). Whereas LKOSirt1 mice exhibited normal levels of fasting and fed blood glucose, inactivation of Sirt1 in DKOIrs1/2 mice (TKOIrs1/2:Sirt1) reduced blood glucose levels and moderately improved systemic glucose tolerance. Pyruvate tolerance was also significantly improved in TKOIrs1/2:Sirt1 mice, suggesting that Sirt1 promotes hepatic gluconeogenesis in this diabetic mouse model. To understand why inactivation of hepatic Sirt1 does not alter blood glucose levels in the wild-type background, we searched for a potential cause and found that expression of small heterodimer partner (SHP, encoded by the Nr0b2 gene), an orphan nuclear receptor, which has been shown to suppress the activity of forkhead transcription factor FoxO1, was decreased in the liver of LKOSirt1 mice. Furthermore, our luciferase reporter assays and chromatin immunoprecipitation analysis revealed that the Nr0b2 gene is a target of FoxO1, which is also regulated by Sirt1. After the gene is upregulated, Nr0b2 can feed back and repress FoxO1- and Sirt1-activated G6pc and Pdk4 gene expression. Thus, our results suggest that Sirt1 can both positively and negatively regulate hepatic gluconeogenesis through FoxO1 and Nr0b2 and keep this physiological process in control.

scholarly journals Sodium Meta-Arsenite Ameliorates Hyperglycemia in Obese Diabeticdb/dbMice by Inhibition of Hepatic Gluconeogenesis

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Young-Sun Lee ◽  
Eun-Kyu Lee ◽  
Hyun-Hee Oh ◽  
Cheol Soo Choi ◽  
Sujong Kim ◽  
...  
Keyword(s):  
Body Weight ◽  
Blood Glucose ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Glucose Production ◽  
Diabetic Mouse ◽  
Hepatic Gluconeogenesis ◽  
Glucose Levels ◽  
Blood Glucose Levels

Sodium meta-arsenite (SA) is implicated in the regulation of hepatic gluconeogenesis-related genesin vitro; however, the effectsin vivohave not been studied. We investigated whether SA has antidiabetic effects in a type 2 diabetic mouse model. Diabeticdb/dbmice were orally intubated with SA (10 mg kg−1body weight/day) for 8 weeks. We examined hemoglobin A1c (HbA1c), blood glucose levels, food intake, and body weight. We performed glucose, insulin, and pyruvate tolerance tests and analyzed glucose production and the expression of gluconeogenesis-related genes in hepatocytes. We analyzed energy metabolism using a comprehensive animal metabolic monitoring system. SA-treated diabeticdb/dbmice had reduced concentrations of HbA1c and blood glucose levels. Exogenous glucose was quickly cleared in glucose tolerance tests. The mRNA expressions of genes for gluconeogenesis-related enzymes, glucose 6-phosphatase (G6Pase), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly reduced in the liver of SA-treated diabeticdb/dbmice. In primary hepatocytes, SA treatment decreased glucose production and the expression of G6Pase, PEPCK, and hepatocyte nuclear factor 4 alpha (HNF-4α) mRNA. Small heterodimer partner (SHP) mRNA expression was increased in hepatocytes dependent upon the SA concentration. The expression of Sirt1 mRNA and protein was reduced, and acetylated forkhead box protein O1 (FoxO1) was induced by SA treatment in hepatocytes. In addition, SA-treated diabeticdb/dbmice showed reduced energy expenditure. Oral intubation of SA ameliorates hyperglycemia indb/dbmice by reducing hepatic gluconeogenesis through the decrease of Sirt1 expression and increase in acetylated FoxO1.

scholarly journals Glycemic variability and cardiovascular disease in patients with type 2 diabetes

2021 ◽  
Vol 9 (1) ◽  
pp. e002032
Author(s):  
Marcela Martinez ◽  
Jimena Santamarina ◽  
Adrian Pavesi ◽  
Carla Musso ◽  
Guillermo E Umpierrez
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Glycated Hemoglobin ◽  
Glucose Monitoring ◽  
Glycemic Variability ◽  
Cardiovascular Complications ◽  
Glucose Levels ◽  
Increased Risk ◽  
Patients With Diabetes

Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.

scholarly journals Altered Glucose and Insulin Responses to Brain Medullary Thyrotropin-Releasing Hormone (TRH)-Induced Autonomic Activation in Type 2 Diabetic Goto-Kakizaki Rats

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5425-5432 ◽  
Author(s):  
Yan Ao ◽  
Natalie Toy ◽  
Moon K. Song ◽  
Vay Liang W. Go ◽  
Hong Yang
Keyword(s):  
Insulin Secretion ◽  
Blood Glucose ◽  
Wistar Rats ◽  
Mrna Levels ◽  
Gk Rats ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Autonomic Activation ◽  
Insulin Responses

Insulin secretion is impaired in type 2 diabetes (T2D). The insulin and glucose responses to central autonomic activation induced by excitation of brain medullary TRH receptors were studied in T2D Goto-Kakizaki (GK) rats. Blood glucose levels in normally fed, pentobarbital-anesthetized GK and nondiabetic Wistar rats were 193 and 119 mg/100 ml in males and 214 and 131 mg/100 ml in females. Intracisternal injection (ic) of the stable TRH analog RX 77368 (10 ng) induced significantly higher insulin response in both genders of overnight-fasted GK rats compared with Wistar rats and slightly increased blood glucose in female Wistar rats but significantly decreased it from 193 to 145 mg/100 ml in female GK rats. RX 77368 (50 ng) ic induced markedly greater glucose and relatively weaker insulin responses in male GK rats than Wistar rats. Bilateral vagotomy blocked ic RX 77368-induced insulin secretion, whereas adrenalectomy abolished its hyperglycemic effect. In adrenalectomized male GK but not Wistar rats, ic RX 77368 (50 ng) dramatically increased serum insulin levels by 6.5-fold and decreased blood glucose levels from 154 to 98 mg/100 ml; these changes were prevented by vagotomy. GK rats had higher basal pancreatic insulin II mRNA levels but a lower response to ic RX 77368 (50 ng) compared with Wistar rats. These results indicate that central-vagal activation-induced insulin secretion is susceptible in T2D GK rats. However, the dominant sympathetic-adrenal response to medullary TRH plays a suppressing role on vagal-mediated insulin secretion. This unbalanced vago-sympathetic activation by medullary TRH may contribute to the impaired insulin secretion in T2D.

scholarly journals PENGARUH JUS LIDAH BUAYA TERHADAP KADAR GLUKOSA DARAH PUASA DAN 2 JAM PP(Post Prandial) PADA PENDERITA DIABETES MELITUS

2019 ◽  
Vol 10 (1) ◽  
pp. 77
Author(s):  
Febria Syafyu Sari ◽  
Ridhyalla Afnuhazi
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Blood Sugar ◽  
Fasting Blood Glucose ◽  
Aloe Vera ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Patients With Diabetes ◽  
Paired T Test ◽  
Diabetes Melitus

ABSTRAK Diabetes Melitus merupakan penyakit yang paling menonjol yang disebabkan oleh gagalnya pengaturan gula darah. Lidah buaya berkhasiat untuk menurunkan kadar gula dalam darah bagi penderita diabetes dan dapat mengontrol tekanan darah. Tujuan penelitian untuk mengetahui pengaruh jus lidah buaya (AloeBarbadensis Miller) terhadap penurunan glukosa darah puasa GDP) dan 2 Jam PP (Post Prendial) pada penderita DM (Diabetes Melitus). Desain penelitian merupakan Quasi Eksperimental dengan pendekatan one group pretest – postest design. Sampel terbagi menjadi 14 responden. Data dianalisis dengan paired t-test. Hasil menunjukan rata-rata penurunan glukosa darah puasa pada intervensi (28,42 gr/dl) dan glukosa darah 2 jam pp pada intervensi (40,57 gr/dl). Untuk analisis bivariat terdapat perbedaan antara glukosa puasa dan 2 jam pp dengan glukosa darah puasa GDP) dan 2 Jam PP (Post Prendial) pada penderita DM (Diabetes Melitus). Kesimpulan didapatkanlidah buaya dapat menurunkan kadar glukosa darah.Berdasarkan hasil penelitian jus lidah buaya dapat menjadi salah satu alternatif keperawatan non farmakologi dalam penyakit diabetes melitus. Kata Kunci : Lidah Buaya ; Diabetes Mellitus THE EFFECT OF VEGETABLE VOCATIONAL JUICE ON FAST BLOOD GLUCOSE LEVELS AND 2 HOURS OF PP (Post Prandial) IN DIABETES MELLITUS  ABSTRACT Diabetes mellitus is the most prominent disease caused by the failure of blood sugar regulation. Aloe vera is efficacious can to  reduce blood sugar levels for diabetics and can control blood pressure. The purpose of this study was to determine the effect of Aloe Barbadensis Miller on the reduction of fasting blood glucose GDP and 2 hours of PP (post prendial) in patients with diabetes mellitus. The research design is Experimental Quasi with one group pretest - postest design approach. The sample is divided into 14 respondents. Data were analyzed by paired t-test. The results showed an average decrease in fasting blood glucose at intervention (28.42 gr / dl) and 2 hours pp blood glucose at intervention (40.57 gr / dl). For bivariate analysis there was a difference between fasting glucose and 2 hours pp with fasting blood glucose GDP) and 2 hours PP (Post Prendial) in patients with diabetes mellitus. The conclusion is that aloe vera can reduce blood glucose levels. Based on the results of research on aloe vera juice can be an alternative non-pharmacological nursing in diabetes mellitus. Keywords: Aloe Vera ; Diabetes Mellitus

TYPE 2 DIABETES MELLITUS;

2018 ◽  
Vol 21 (05) ◽  
pp. 1005-1014
Author(s):  
Jamil A. Malik ◽  
Tuba Mumtaz ◽  
Samsaam Ali Haider
Keyword(s):  
Blood Glucose ◽  
Emotional Problem ◽  
Emotional Problems ◽  
Treatment Modalities ◽  
Routine Practice ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Obese Class ◽  
Patients With Diabetes ◽  
Effective Instrument

Objectives: The study is aimed to assess emotional problem of patients with Type2diabetes by translating and validating PAID. Associations between PAID and blood glucoselevels, and differences in prevalence of emotional problems across treatment modalities andBMI. Data Sources: Data was collected from various outpatients of Rawalpindi and Islamabad.Sample and Procedure: The sample of study comprised of 300 patients with diabetes bothmale = 135 (45%) and female n=165 (55%). Formal approval was taken from authorities atrespective hospitals and after taking informed consent patients were interviewed. Period:Data collection was completed during Feb to April, 2013. Material and Method: Patients wereasked to fill in demographic sheet along with Translated PAID scale. Latest blood glucose levelswere collected from their medical records whereas BMI was calculated by measuring patients’weight and height. Results: Results showed that emotional problems as assessed by PAID arepositively correlated with blood glucose levels (r=.12 to r=.19, p<.05). Additionally, patientswith IV modality of treatment (i.e., taking insulin shots) suffered significantly high (MD=4.88,p=.01) from emotional problems and patients with normal BMI and Obese Class-II have are athigher risk of emotional problem. Finally, patients rated serious concerns on diabetes-relatedissues like lifelong maintenance, future complications, depression and anxiety, and satisfactionwith physician. Conclusions: PAID is a very effective instrument in identifying emotionalproblems of diabetes patients related to adherence and compliance to their treatment regimeand hence it shall be used by physicians and health professional in routine practice.

Hypoglycaemia in the treatment of diabetes mellitus

2011 ◽  
pp. 1849-1861
Author(s):  
Pratik Choudhary ◽  
Stephanie A. Amiel
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Blood Glucose Concentration ◽  
Cerebral Metabolism ◽  
Chronic Complications ◽  
Glucose Levels ◽  
Patients With Diabetes ◽  
Treatment Of Diabetes ◽  
Clinically Significant ◽  
The Brain

Hypoglycaemia (low blood glucose concentration) is the most important acute complication of the pharmacological treatment of diabetes mellitus. Low blood glucose impairs brain (and, potentially, cardiac) function. The brain has minimal endogenous stores of energy, with small amounts of glycogen in astroglial cells. The brain is therefore largely dependent on circulating glucose as the substrate to fuel cerebral metabolism and support cognitive performance. If blood glucose levels fall sufficiently, cognitive dysfunction is inevitable. In health, efficient glucose sensing and counterregulatory mechanisms exist to prevent clinically significant hypoglycaemia. These are impaired by diabetes and by its therapies. Patients with diabetes rank fear of hypoglycaemia as highly as fear of chronic complications such as nephropathy or retinopathy (1). Fear of hypoglycaemia, hypoglycaemia itself and attempts to avoid hypoglycaemia limit the degree to which glycaemic control can be intensified to reduce the risk of chronic complications of diabetes both for type 1 and type 2 diabetes.

scholarly journals Prototypes of User Interfaces for Mobile Applications for Patients with Diabetes

Computers ◽  
2018 ◽  
Vol 8 (1) ◽  
pp. 1 ◽  
Author(s):  
Jan Pavlas ◽  
Ondrej Krejcar ◽  
Petra Maresova ◽  
Ali Selamat
Keyword(s):  
Blood Glucose ◽  
User Interfaces ◽  
Mobile Applications ◽  
Eating Habits ◽  
Relevant Literature ◽  
Optimal Solution ◽  
Glucose Levels ◽  
Current State ◽  
Blood Glucose Levels ◽  
Patients With Diabetes

We live in a heavily technologized global society. It is therefore not surprising that efforts are being made to integrate current information technology into the treatment of diabetes mellitus. This paper is dedicated to improving the treatment of this disease through the use of well-designed mobile applications. Our analysis of relevant literature sources and existing solutions has revealed that the current state of mobile applications for diabetics is unsatisfactory. These limitations relate both to the content and the Graphical User Interface (GUI) of existing applications. Following the analysis of relevant studies, there are four key elements that a diabetes mobile application should contain. These elements are: (1) blood glucose levels monitoring; (2) effective treatment; (3) proper eating habits; and (4) physical activity. As the next step in this study, three prototypes of new mobile applications were designed. Each of the prototypes represents one group of applications according to a set of given rules. The most optimal solution based on the users’ preferences was determined by using a questionnaire survey conducted with a sample of 30 respondents participating in a questionnaire after providing their informed consent. The age of participants was from 15 until 30 years old, where gender was split to 13 males and 17 females. As a result of this study, the specifications of the proposed application were identified, which aims to respond to the findings discovered in the analytical part of the study, and to eliminate the limitations of the current solutions. All of the respondents expressed preference for an application that includes not only the key functions, but a number of additional functions, namely synchronization with one of the external devices for measuring blood glucose levels, while five-sixths of them found suggested additional functions as being sufficient.

scholarly journals Discrepancies Between Blood Glucose and Interstitial Glucose—Technological Artifacts or Physiology: Implications for Selection of the Appropriate Therapeutic Target

2017 ◽  
Vol 11 (4) ◽  
pp. 766-772 ◽  
Author(s):  
Thorsten Siegmund ◽  
Lutz Heinemann ◽  
Ralf Kolassa ◽  
Andreas Thomas
Keyword(s):  
Blood Glucose ◽  
Therapeutic Target ◽  
Diabetes Management ◽  
Glucose Monitoring ◽  
Blood Glucose Measurement ◽  
Glucose Measurement ◽  
Glucose Levels ◽  
Therapeutic Decisions ◽  
The Impact ◽  
Selection Of

Background: For decades, the major source of information used to make therapeutic decisions by patients with diabetes has been glucose measurements using capillary blood samples. Knowledge gained from clinical studies, for example, on the impact of metabolic control on diabetes-related complications, is based on such measurements. Different to traditional blood glucose measurement systems, systems for continuous glucose monitoring (CGM) measure glucose in interstitial fluid (ISF). The assumption is that glucose levels in blood and ISF are practically the same and that the information provided can be used interchangeably. Thus, therapeutic decisions, that is, the selection of insulin doses, are based on CGM system results interpreted as though they were blood glucose values. Methods: We performed a more detailed analysis and interpretation of glucose profiles obtained with CGM in situations with high glucose dynamics to evaluate this potentially misleading assumption. Results: Considering physical activity, hypoglycemic episodes, and meal-related differences between glucose levels in blood and ISF uncover clinically relevant differences that can make it risky from a therapeutic point of view to use blood glucose for therapeutic decisions. Conclusions: Further systematic and structured evaluation as to whether the use of ISF glucose is more safe and efficient when it comes to acute therapeutic decisions is necessary. These data might also have a higher prognostic relevance when it comes to long-term metabolic consequences of diabetes. In the long run, it may be reasonable to abandon blood glucose measurements as the basis for diabetes management and switch to using ISF glucose as the appropriate therapeutic target.

Effectiveness of acarbose in treating elderly patients with diabetes with postprandial hypotension

2017 ◽  
Vol 65 (4) ◽  
pp. 772-783 ◽  
Author(s):  
Jie Zhang ◽  
Lixin Guo
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Elderly Patients ◽  
Controlled Trial ◽  
Clinical Trial Registry ◽  
Postprandial Hypotension ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Patients With Diabetes ◽  
Group B

Postprandial hypotension (PPH) is a common condition that occurs primarily in elderly patients with type 2 diabetes mellitus (T2DM). This study aimed to assess the effectiveness of acarbose for PPH; it also investigated possible mechanisms behind PPH development. This single-blind, randomized controlled trial included 91 elderly patients with T2DM, aged between 60 and 80 years, who were inpatients at Beijing Hospital between March 2012 and November 2014. The patients were included into one of three groups: Group A, patients with T2DM without PPH; Group B, patients with T2DM with PPH receiving placebo; and Group C, patients with T2DM with PPH receiving acarbose. After an overnight fast, patients received a single dose of acarbose (100 mg) or placebo and then consumed a standardized 450 kcal meal. Blood pressure, glucose levels, heart rate (HR), and catecholamine levels were evaluated. Acarbose ameliorated PPH as determined by significant improvements in the duration and maximal fall in blood pressure (both p<0.001); however, no differences in HR and blood glucose levels were observed. In patients with PPH, blood pressure was correlated with blood glucose and HR variability values (p<0.05). Correlations between epinephrine and glucagon-like peptide-1 with blood pressure in groups A and C were largely lost in group B. Acarbose reduced postprandial blood pressure fluctuations in elderly patients with diabetes. PPH may be related to impaired autonomic nervous system function, reduced catecholamine secretion, and postprandial fluctuations in blood glucose levels.Trial registration numberChinese Clinical Trial Registry ChiCTR-IPR-15006177.

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