Vildagliptin/pioglitazone combination improved the overall glycemic control in type I diabetic rats

2018 ◽  
Vol 96 (8) ◽  
pp. 710-718 ◽  
Author(s):  
Amir Mohamed Abdelhamid ◽  
Rania Ramadan Abdelaziz ◽  
Hatem Abdelrahman Ali Salem
Keyword(s):  
Glycemic Control ◽  
Type I Diabetes ◽  
Serum Insulin ◽  
Immunohistochemical Analysis ◽  
Diabetic Rats ◽  
Suboptimal Control ◽  
Type I ◽  
Β Cells ◽  
Treatment Regimens ◽  
Glucose Levels

Type I diabetes (TID) is generally assumed to be caused by an immune associated, if not directly immune-mediated, destruction of pancreatic β-cells. In patients with long-term diabetes, the pancreas lacks insulin-producing cells and the residual β-cells are unable to regenerate. Patients with TID are subjected to a lifelong insulin therapy which shows risks of hypoglycemia, suboptimal control and ketosis. In this study, we investigated the potential role of vildagliptin (Vilda) alone or in combination with pioglitazone (Pio), as treatment regimens for TID using streptozotocin (STZ)-induced TID model in rats. Daily oral administration of Vilda (5 mg/kg) alone or in combination with Pio (20 mg/kg) for 7 weeks significantly reduced blood glucose levels and HbA1c. It increased serum insulin levels and decreased serum glucagon. It also showed a strong antioxidant activity. Immunohistochemical analysis showed a marked improvement in β-cells in treated groups when compared with the diabetic group, which appeared in the normal cellular and architecture restoration of β-cells in the islets of Langerhans. Vilda alone or in combination with Pio has the ability to improve the overall glycemic control in type I diabetic rats and may be considered a hopeful and effective remedy for TID.

scholarly journals Integration of Islet/Beta-Cell Transplants with Host Tissue Using Biomaterial Platforms

Endocrinology ◽  
2020 ◽  
Vol 161 (11) ◽  
Author(s):  
Daniel W Clough ◽  
Jessica L King ◽  
Feiran Li ◽  
Lonnie D Shea
Keyword(s):  
Stem Cell ◽  
Immune Responses ◽  
Cell Function ◽  
Type I Diabetes ◽  
Glucose Sensing ◽  
Trophic Factors ◽  
Design Parameters ◽  
Type I ◽  
Β Cells ◽  
Glucose Levels

Abstract Cell-based therapies are emerging for type I diabetes mellitus (T1D), an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells, as a means to provide long-term restoration of glycemic control. Biomaterial scaffolds provide an opportunity to enhance the manufacturing and transplantation of islets or stem cell–derived β-cells. In contrast to encapsulation strategies that prevent host contact with the graft, recent approaches aim to integrate the transplant with the host to facilitate glucose sensing and insulin distribution, while also needing to modulate the immune response. Scaffolds can provide a supportive niche for cells either during the manufacturing process or following transplantation at extrahepatic sites. Scaffolds are being functionalized to deliver oxygen, angiogenic, anti-inflammatory, or trophic factors, and may facilitate cotransplantation of cells that can enhance engraftment or modulate immune responses. This local engineering of the transplant environment can complement systemic approaches for maximizing β-cell function or modulating immune responses leading to rejection. This review discusses the various scaffold platforms and design parameters that have been identified for the manufacture of human pluripotent stem cell–derived β-cells, and the transplantation of islets/β-cells to maintain normal blood glucose levels.

Lessons on autoimmune diabetes from animal models

2006 ◽  
Vol 110 (6) ◽  
pp. 627-639 ◽  
Author(s):  
Yang Yang ◽  
Pere Santamaria
Keyword(s):  
Animal Models ◽  
Autoimmune Diabetes ◽  
Type I Diabetes ◽  
Vascular Complications ◽  
Diabetic Mouse ◽  
Suboptimal Control ◽  
Type I ◽  
Genetic Elements ◽  
Glucose Levels ◽  
Islet Inflammation

T1DM (Type I diabetes mellitus) results from selective destruction of the insulin-producing β-cells of the pancreas by the immune system, and is characterized by hyperglycaemia and vascular complications arising from suboptimal control of blood glucose levels. The discovery of animal models of T1DM in the late 1970s and early 1980s, particularly the NOD (non-obese diabetic) mouse and the BB (BioBreeding) diabetes-prone rat, had a fundamental impact on our ability to understand the genetics, aetiology and pathogenesis of this disease. NOD and BB diabetes-prone rats spontaneously develop a form of diabetes that closely resembles the human counterpart. Early studies of these animals quickly led to the realization that T1DM is caused by autoreactive T-lymphocytes and revealed that the development of T1DM is controlled by numerous polymorphic genetic elements that are scattered throughout the genome. The development of transgenic and gene-targeting technologies during the 1980s allowed the generation of models of T1DM of reduced genetic and pathogenic complexity, and a more detailed understanding of the immunogenetics of T1DM. In this review, we summarize the contribution of studies in animal models of T1DM to our current understanding of four fundamental aspects of T1DM: (i) the nature of genetic elements affording T1DM susceptibility or resistance; (ii) the mechanisms underlying the development and recruitment of pathogenic autoreactive T-cells; (iii) the identity of islet antigens that contribute to the initiation and/or progression of islet inflammation and β-cell destruction; and (iv) the design of avenues for therapeutic intervention that are rooted in the knowledge gained from studies of animal models. Development of new animal models will ensure continued progress in these four areas.

Insulin-sparing effect of hydroxychloroquine in diabetic rats is concentration dependent

1999 ◽  
Vol 77 (2) ◽  
pp. 118-123 ◽  
Author(s):  
Jaber Emami ◽  
Hertzel C Gerstein ◽  
Franco M Pasutto ◽  
Fakhreddin Jamali
Keyword(s):  
Therapeutic Potential ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Diabetic Rats ◽  
Type I ◽  
Time Curve ◽  
Insulin Metabolism ◽  
Glucose Levels ◽  
Percent Change ◽  
Glucose Challenge

To study the effect of hydroxychloroquine (HCQ) on glucose and insulin homeostasis, healthy rats were dosed with160 mg·kg-1·day-1 of HCQ orally, and streptozocin-induced diabetic rats received 80, 120, and 160 mg·kg-1·day-1 of HCQ, while controls received normal saline. Ten days after treatment with HCQ, healthy animals were challenged intravenously with insulin or glucose, while diabetic rats were given only an i.v. injection of insulin. In healthy rats, the areas within and under the glucose concentration - time curve following insulin and glucose challenge were estimated. In diabetic animals, the areas under the curve for both the percent change in serum glucose from baseline (AUG) and the percent change in serum insulin from baseline (AUI) were used as pharmacodynamic end points. In healthy rats, HCQ did not influence fasting serum glucose concentrations or glycemic profiles following i.v. administration of glucose or insulin. In diabetic rats, AUG and AUI were increased dependent on blood HCQ concentrations. The normal homeostatic mechanisms responsible for insulin-glucose regulation may compensate for possible HCQ-induced reduction of insulin metabolism in healthy rats. The HCQ dose- or concentration-effect relationships for glucose and insulin were linear over the range of HCQ concentrations tested. It is concluded that HCQ significantly elevated insulin blood concentration resulting in reduced glucose levels in a concentration-dependent fashion in diabetic rats. HCQ may have therapeutic potential in the treatment of type I and type II diabetes.Key words: hydroxychloroquine, enantiomers, insulin, glucose, diabetes, pharmacokinetics.

Effects of long-term optimization and short-term deterioration of glycemic control on glucose counterregulation in type I diabetes mellitus

Diabetes ◽  
1984 ◽  
Vol 33 (4) ◽  
pp. 394-400 ◽  
Author(s):  
G. Bolli ◽  
P. De Feo ◽  
S. De Cosmo ◽  
G. Perriello ◽  
G. Angeletti ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Type I Diabetes ◽  
Type I Diabetes Mellitus ◽  
Type I ◽  
Short Term

Antidiabetic effect of Psychotria malayana Jack in induced type 1 diabetic rat

MEDISAINS ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 19
Author(s):  
Fairuz Fairuz ◽  
Hasna Dewi ◽  
Humaryanto Humaryanto
Keyword(s):  
Blood Glucose ◽  
Side Effects ◽  
Type I Diabetes ◽  
Langerhans Cell ◽  
Diabetic Rat ◽  
Type I ◽  
Antidiabetic Effect ◽  
Glucose Levels ◽  
Blood Glucose Levels

Background: Therapies for hyperglycemic treatment, including insulin and oral diabetes medications, have been confirmed to cause several side effects. Thus, finding new drugs with fewer side effects is of high importance. Salung leaf herb (Psychotria malayana Jack) reported used in traditional societies as a treatment for diabetes. However, the scientific proof of this plant for diabetes treatment is still lacking.Objective: To evaluate the antidiabetic effect of the P. malayana jack in induced type 1 diabetic rats by assessing blood glucose level and pancreatic cells in white rats.Methods: Alloxan used to induce type I diabetes. Rats randomly divided into six groups. A Group P1 received 250 mg/kg BW; group P2 received 500 mg/kg BW, group P3 received 1000 mg/kg BW. While group 4 basal received no treatment, group 5 received distilled water as a negative control, and group 6 received glibenclamide as a positive control. Medications are given for six days. Glucose levels were measured, and observation of pancreatic Langerhans cell damages.Results:  A decrease in blood glucose levels observed in all treatment groups. The most significant reduction (49.76%; 1000 mg/kg BW) occurred in the P3 group. Morphological features of pancreatic Langerhans cell damage were slightly high in the P1 group.Conclusion: P. malayana Jack can consider having an antidiabetic effect in a type 1 diabetic rat by reducing blood glucose levels.

scholarly journals Periodontal disease and type I diabetes mellitus: Associations with glycemic control and complications

2013 ◽  
Vol 17 (5) ◽  
pp. 597 ◽  
Author(s):  
Ajita Meenawat ◽  
Karan Punn ◽  
Vivek Srivastava ◽  
AnandS Meenawat ◽  
RS Dolas ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Glycemic Control ◽  
Periodontal Disease ◽  
Type I Diabetes ◽  
Type I Diabetes Mellitus ◽  
Type I

Type I Diabetes Mellitus

2019 ◽  
Author(s):  
Joseph I. Wolfsdorf ◽  
Katharine Garvey
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Glycemic Control ◽  
Type 1 Diabetes Mellitus ◽  
Diabetic Ketoacidosis ◽  
Autoimmune Diabetes ◽  
Type I ◽  
Insulin Deficiency ◽  
Glucose Levels

Type 1 diabetes mellitus is characterized by severe insulin deficiency, making patients dependent on exogenous insulin replacement for survival. These patients can experience life-threatening events when their glucose levels are significantly abnormal. Type 1 diabetes accounts for 5 to 10% of all diabetes cases, with type 2 accounting for most of the remainder. This review details the pathophysiology, stabilization and assessment, diagnosis and treatment, disposition and outcomes of patients with Type 1 diabetes mellitus. Figures show the opposing actions of insulin and glucagon on substrate flow and plasma levels; plasma glucose, insulin and C-peptide levels throughout the day; the structure of human proinsulin; current view of the pathogenesis of Type 1 autoimmune diabetes mellitus; pathways that lead from insulin deficiency to the major clinical manifestations of Type 1 diabetes mellitus; relationship between hemoglobin A1c values at the end of a 3-month period and calculated average glucose levels during the 3-month period; different combinations of various insulin preparations used to establish glycemic control; and basal-bolus and insulin pump regimens. Tables list the etiologic classification of Type 1 diabetes mellitus, typical laboratory findings and monitoring in diabetic ketoacidosis, criteria for the diagnosis of Type 1 diabetes, clinical goals of Type 1 diabetes treatment, and insulin preparations. This review contains 10 figures, 9 tables, and 40 references. Keywords: Type 1 diabetes mellitus, optimal glycemic control, hypoglycemia, hyperglycemia, polyuria, polydipsia, polyphagia, HbA1c, medical nutrition therapy, Diabetic Ketoacidosis

scholarly journals Influence of GABA and GABA-producing Lactobacillus brevis DPC 6108 on the development of diabetes in a streptozotocin rat model

2016 ◽  
Vol 7 (3) ◽  
pp. 409-420 ◽  
Author(s):  
T.M. Marques ◽  
E. Patterson ◽  
R. Wall ◽  
O. O’Sullivan ◽  
G.F. Fitzgerald ◽  
...  
Keyword(s):  
Body Weight ◽  
Serum Insulin ◽  
Lactobacillus Brevis ◽  
Diabetic Rats ◽  
Protective Effects ◽  
Sprague Dawley ◽  
Metabolic Markers ◽  
Glucose Levels ◽  
Intestinal Length ◽  
Sprague Dawley Rats

The aim of this study was to investigate if dietary administration of γ-aminobutyric acid (GABA)-producing Lactobacillus brevis DPC 6108 and pure GABA exert protective effects against the development of diabetes in streptozotocin (STZ)-induced diabetic Sprague Dawley rats. In a first experiment, healthy rats were divided in 3 groups (n=10/group) receiving placebo, 2.6 mg/kg body weight (bw) pure GABA or L. brevis DPC 6108 (~109microorganisms). In a second experiment, rats (n=15/group) were randomised to five groups and four of these received an injection of STZ to induce type 1 diabetes. Diabetic and non-diabetic controls received placebo [4% (w/v) yeast extract in dH2O], while the other three diabetic groups received one of the following dietary supplements: 2.6 mg/kg bw GABA (low GABA), 200 mg/kg bw GABA (high GABA) or ~109 L. brevis DPC 6108. L. brevis DPC 6108 supplementation was associated with increased serum insulin levels (P<0.05), but did not alter other metabolic markers in healthy rats. Diabetes induced by STZ injection decreased body weight (P<0.05), increased intestinal length (P<0.05) and stimulated water and food intake. Insulin was decreased (P<0.05), whereas glucose was increased (P<0.001) in all diabetic groups, compared with non-diabetic controls. A decrease (P<0.01) in glucose levels was observed in diabetic rats receiving L. brevis DPC 6108, compared with diabetic-controls. Both the composition and diversity of the intestinal microbiota were affected by diabetes. Microbial diversity in diabetic rats supplemented with low GABA was not reduced (P>0.05), compared with non-diabetic controls while all other diabetic groups displayed reduced diversity (P<0.05). L. brevis DPC 6108 attenuated hyperglycaemia induced by diabetes but additional studies are needed to understand the mechanisms involved in this reduction.

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