Improved Diabetes Control and Pancreatic Function in a Type 2 Diabetic after Omeprazole Administration

A 43-year-old man with type 2 diabetes, opposed to insulin use and poorly responsive to oral agents added sequentially over 6 years, was placed on 40 mg omeprazole twice daily. A linear decline in daily fasting blood glucose was observed over the first two-month treatment, and his hemoglobin A1c was reduced from 11.9% to 8.2%, then sustained at 8.1% after four months. Glucose, insulin, and C-peptide response to a 2-hour glucose tolerance test were consistently improved across this time period, and calculated beta-cell mass increased by 67%. We believe these responses are consistent with activation or neogenesis of pancreatic beta cells, possibly through a gastrin-mediated mechanism.

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Antidiabetic and Antiobesity Effects of Artemether in db/db Mice

BioMed Research International ◽

10.1155/2018/8639523 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Yu Guo ◽

Wei Fu ◽

Yakai Xin ◽

Jinlei Bai ◽

Huifang Peng ◽

...

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Food Intake ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Fasting Blood Glucose ◽

Tolerance Test ◽

Tunel Staining ◽

Intragastric Administration

This study is designed to investigate the effect of artemether on type 2 diabetic db/db mice. The experiments consisted of three groups: normal control (NC, db/+, 1% methylcellulose, intragastric administration), diabetic control (DM, db/db, 1% methylcellulose, intragastric administration), and artemether treated (artemether, db/db, 200 mg/kg of artemether, intragastric administration). The treatment lasted for two weeks. The food intake, body weight, and fasting blood glucose of mice were measured every three days. At the start and end of the experiment, the intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (IPITT) were performed. We determined the serum insulin and glucagon levels by ELISA kits and calculated insulin resistance index (HOME-IR). HE staining was used to observe the morphologies of pancreas and liver in mice. The damage of pancreatic beta cells was evaluated by TUNEL staining and immunofluorescence. We found the following: (1) compared with the DM group, the food intake and weight increase rate of artemether group significantly reduced (P<0.05); (2) compared with pretreatment, artemether significantly reduced the fasting blood glucose levels, and the areas under the curves (AUCs) of IPGTT were decreased significantly, increasing the tolerance to glucose of db/db mice. (P<0.05); (3) artemether improved hyperinsulinemia and decreased the AUCs of IPITT and HOME-IR, increasing the insulin sensitivity of db/db mice. (4) Artemether significantly ameliorated islet vacuolar degeneration and hepatic steatosis in db/db mice. (5) Artemether reduced the apoptosis of pancreatic beta cells and increased insulin secretion in db/db mice compared with DM group (P<0.05). Our results indicated that artemether significantly improved glucose homeostasis and insulin resistance and had the potential activity to prevent obesity, reduced the severity of fatty liver, and protected pancreatic beta cells, promising to treat type 2 diabetes.

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2144-P: Early Administration of Dapagliflozin Preserves Pancreatic Beta-Cell Mass through an Epigenetic Modification in a Mouse Model of Type 2 Diabetes

Diabetes ◽

10.2337/db19-2144-p ◽

2019 ◽

Vol 68 (Supplement 1) ◽

pp. 2144-P

Author(s):

SHUN-ICHIRO ASAHARA ◽

AYUMI KANNO ◽

YOSHIAKI KIDO

Keyword(s):

Type 2 Diabetes ◽

Mouse Model ◽

Beta Cell ◽

Epigenetic Modification ◽

Pancreatic Beta Cell ◽

Cell Mass ◽

Beta Cell Mass ◽

Early Administration ◽

Pancreatic Beta Cell Mass

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Cinammon (Cinnamomum Spp.) and Type 2 Diabetes Mellitus

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.18:247-255 ◽

2019 ◽

Vol 18 (3) ◽

pp. 247-255

Author(s):

Sierra-Puente D. ◽

Abadi-Alfie S. ◽

Arakanchi-Altaled K. ◽

Bogard-Brondo M. ◽

García-Lascurain M. ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Systematic Reviews ◽

Meta Analysis ◽

Fasting Blood Glucose ◽

Tolerance Test ◽

Oral Glucose ◽

Key Aspects

Spices such as cinnamon (Cinnamomum Spp.) have been of interest due to their phytochemical composition that exert hypoglycemic effects with potential for management of type 2 diabetes mellitus (T2DM). We summarize data from 27 manuscripts that include, one book chapter, 3 review articles, 10 randomized controlled trials, 4 systematic reviews with meta-analysis, and 9 preclinical studies. The most frequently used cinnamon variety was Cinnamomum cassia rather than the Cinnamomum zeylanicum, whereas outcomes were defined as fasting blood glucose, glycated hemoglobin, and oral glucose tolerance test. A great variability in methodology such as different doses (from 120 mg to 6 g), duration of intervention, data retrieved and use of different concomitant medication, were found to be key aspects of most of trials and systematic reviews with meta-analysis available to date. Low quality studies have been made in most cases with a lot of heterogeneity clouding significance of results. More research needs to be done in order to yield accurate evidence for evidence-based recommendations. Its use is not currently a reliable nor advisable option for the treatment of T2DM.

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Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice

Pharmacology ◽

10.1159/000478909 ◽

2017 ◽

Vol 100 (5-6) ◽

pp. 218-228 ◽

Cited By ~ 2

Author(s):

Mu-chao Wu ◽

Wei-ran Ye ◽

Yi-jia Zheng ◽

Shan-shan Zhang

Keyword(s):

Blood Lactate ◽

Cell Mass ◽

Lactate Production ◽

Beta Cell Mass ◽

Serum Lactate ◽

Blood Levels ◽

Anti Inflammatory ◽

Lactate Levels ◽

Blood Lactate Levels

Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice. These results show that OXA enhances the anti-inflammatory and insulin-sensitizing effects of MET through the inhibition of tissue lactate production in db/db mice.

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Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells

Biomolecules ◽

10.3390/biom12010104 ◽

2022 ◽

Vol 12 (1) ◽

pp. 104

Author(s):

Elisa Fernández-Millán ◽

Carlos Guillén

Keyword(s):

Beta Cell ◽

Beta Cells ◽

Cell Biology ◽

Pancreatic Beta Cells ◽

Metabolic Diseases ◽

Cell Function ◽

Cell Mass ◽

Beta Cell Mass ◽

Short Chain Fatty Acids

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells communicate with metabolic and non-metabolic tissues provides a novel area for investigation and implicates the importance of inter-organ communication in the pathology of metabolic diseases such as T2D. In this review, we provide an overview of secreted factors from diverse organs and tissues that have been shown to impact beta-cell biology. Specifically, we discuss experimental and clinical evidence in support for a role of gut to beta-cell crosstalk, paying particular attention to bacteria-derived factors including short-chain fatty acids, lipopolysaccharide, and factors contained within extracellular vesicles that influence the function and/or the survival of beta cells under normal or diabetogenic conditions.

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Update on the Protective Molecular Pathways Improving Pancreatic Beta-Cell Dysfunction

Mediators of Inflammation ◽

10.1155/2013/750540 ◽

2013 ◽

Vol 2013 ◽

pp. 1-14 ◽

Cited By ~ 14

Author(s):

Alessandra Puddu ◽

Roberta Sanguineti ◽

François Mach ◽

Franco Dallegri ◽

Giorgio Luciano Viviani ◽

...

Keyword(s):

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Cell Function ◽

Pancreatic Beta Cell ◽

Cell Mass ◽

Beta Cell Mass ◽

Beta Cell Dysfunction ◽

Molecular Pathways ◽

Cell Dysfunction

The primary function of pancreatic beta-cells is to produce and release insulin in response to increment in extracellular glucose concentrations, thus maintaining glucose homeostasis. Deficient beta-cell function can have profound metabolic consequences, leading to the development of hyperglycemia and, ultimately, diabetes mellitus. Therefore, strategies targeting the maintenance of the normal function and protecting pancreatic beta-cells from injury or death might be crucial in the treatment of diabetes. This narrative review will update evidence from the recently identified molecular regulators preserving beta-cell mass and function recovery in order to suggest potential therapeutic targets against diabetes. This review will also highlight the relevance for novel molecular pathways potentially improving beta-cell dysfunction.

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Dynamic Regulation of JAK-STAT Signaling Through the Prolactin Receptor Predicted by Computational Modeling

Cellular and Molecular Bioengineering ◽

10.1007/s12195-020-00647-8 ◽

2020 ◽

Author(s):

Ryland D. Mortlock ◽

Senta K. Georgia ◽

Stacey D. Finley

Keyword(s):

Experimental Data ◽

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Prolactin Receptor ◽

Cell Mass ◽

Beta Cell Mass ◽

Receptor Internalization ◽

Proliferative Potential ◽

Stat Signaling

Abstract Introduction The expansion of insulin-producing beta cells during pregnancy is critical to maintain glucose homeostasis in the face of increasing insulin resistance. Prolactin receptor (PRLR) signaling is one of the primary mediators of beta cell expansion during pregnancy, and loss of PRLR signaling results in reduced beta cell mass and gestational diabetes. Harnessing the proliferative potential of prolactin signaling to expand beta cell mass outside of the context of pregnancy requires quantitative understanding of the signaling at the molecular level. Methods A mechanistic computational model was constructed to describe prolactin-mediated JAK-STAT signaling in pancreatic beta cells. The effect of different regulatory modules was explored through ensemble modeling. A Bayesian approach for likelihood estimation was used to fit the model to experimental data from the literature. Results Including receptor upregulation, with either inhibition by SOCS proteins, receptor internalization, or both, allowed the model to match experimental results for INS-1 cells treated with prolactin. The model predicts that faster dimerization and nuclear import rates of STAT5B compared to STAT5A can explain the higher STAT5B nuclear translocation. The model was used to predict the dose response of STAT5B translocation in rat primary beta cells treated with prolactin and reveal possible strategies to modulate STAT5 signaling. Conclusions JAK-STAT signaling must be tightly controlled to obtain the biphasic response in STAT5 activation seen experimentally. Receptor up-regulation, combined with SOCS inhibition, receptor internalization, or both is required to match experimental data. Modulating reactions upstream in the signaling can enhance STAT5 activation to increase beta cell survival.

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Wisp1 is a circulating factor that stimulates proliferation of adult mouse and human beta cells

Nature Communications ◽

10.1038/s41467-020-19657-1 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Rebeca Fernandez-Ruiz ◽

Ainhoa García-Alamán ◽

Yaiza Esteban ◽

Joan Mir-Coll ◽

Berta Serra-Navarro ◽

...

Keyword(s):

Beta Cell ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Cell Mass ◽

Beta Cell Mass ◽

Beta Cell Proliferation ◽

Cell Replication ◽

Trophic Effect ◽

Beta Cell Replication

AbstractExpanding the mass of pancreatic insulin-producing beta cells through re-activation of beta cell replication has been proposed as a therapy to prevent or delay the appearance of diabetes. Pancreatic beta cells exhibit an age-dependent decrease in their proliferative activity, partly related to changes in the systemic environment. Here we report the identification of CCN4/Wisp1 as a circulating factor more abundant in pre-weaning than in adult mice. We show that Wisp1 promotes endogenous and transplanted adult beta cell proliferation in vivo. We validate these findings using isolated mouse and human islets and find that the beta cell trophic effect of Wisp1 is dependent on Akt signaling. In summary, our study reveals the role of Wisp1 as an inducer of beta cell replication, supporting the idea that the use of young blood factors may be a useful strategy to expand adult beta cell mass.

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