pectins and Diabetes-Mellitus--Type-1

Intestinal homeostasis underpins the development of type 1 diabetes (T1D), and dietary manipulations to enhance intestinal homeostasis have been proposed to prevent T1D. The current study aimed to investigate the efficacy of supplementing a novel specific low-methoxyl pectin (LMP) dietary fiber in preventing T1D development. Female NOD mice were weaned onto control or 5% (wt/wt) LMP supplemented diets for up to 40 weeks of age, overt diabetes incidence and blood glucose were monitored. Then broad-spectrum antibiotics (ABX) treatment per os for 7 days followed by gut microbiota transfer was performed to demonstrate gut microbiota-dependent effects. Next-generation sequencing was used for analyzing the composition of microbiota in caecum. Concentration of short chain fatty acids were determined by GC-MS. The barrier reinforcing tight junction proteins zonula occludens-2 (ZO-2), claudin-1 and NOD like receptor protein 3 (NLRP3) inflammasome activation were determined by Western blot. The proportion of CD25

Topics: Animals; Cecum; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Female; Gastrointestinal Microbiome; Humans; Mice; Mice, Inbred NOD; Pancreas; Pectins; T-Lymphocytes, Regulatory

This study aims to examine the protective effects of specific low-methoxyl pectin (LMP) on the development of type 1 diabetes (T1D).. Female non-obese diabetic (NOD) mice are weaned onto either control or 5% LMP supplemented diets for up to 22 weeks of age. T1D incidence, gut barrier function, and pancreatic-gut immune responses are analyzed. LMP supplementation significantly dampened the onset of T1D in NOD mice. LMP supplementation induces caecal homeostasis, as indicated by the increasing SCFAs production, higher expression of tight junction proteins claudin 1, zonula occludens-2 in caecum. Furthermore, LMP-mediated caecal homeostasis impacts gut-pancreatic immunity, as evidenced by increased regulatory T cell population, modulated inflammatory cytokine expression, and suppressed NOD like receptor protein 3 (NLRP3) inflammasome activation in both caecum and pancreas.. The data demonstrate that LMP limits T1D development by inducing caecal homeostasis to shape pancreatic immune environment, providing a scientific basis for using LMP as a novel functional supplementation to intervene T1D.

Topics: Animals; Cecum; Diabetes Mellitus, Type 1; Dietary Supplements; Fatty Acids, Volatile; Female; Hypoglycemic Agents; Immunologic Factors; Intestines; Mice, Inbred NOD; NLR Family, Pyrin Domain-Containing 3 Protein; Pancreas; Pectins; T-Lymphocytes, Regulatory

Cardiovascular complications are among the leading causes of morbidity and mortality in diabetes mellitus. Despite the beneficial effects of subcutaneous insulin, reports suggest that the therapy itself precipitates cardiovascular risks due to the high insulin concentration administered. It is therefore necessary to seek alternative routes of insulin administration that may bypass the undesirable effects associated with high plasma insulin concentrations. Accordingly, the present study investigated the effects of a novel transdermal pectin-insulin patch on selected markers of cardiovascular function in diabetes.. Pectin-insulin matrix patches (20.0, 40.8, and 82.9 μg/kg) were prepared as described previously. The three formulations were applied to streptozotocin-induced diabetic rats thrice daily. Blood glucose concentrations and mean arterial pressure (MAP) were monitored weekly for 5 weeks. Rats were then killed and blood collected for analysis of the lipid profile, cardiotropin-1, tumor necrosis factor (TNF)-α, and high-sensitivity C-reactive protein (hsCRP).. The patches decreased blood glucose concentrations and diabetes-induced disturbances in lipid profile were attenuated by patch application (82.9 μg/kg). The diabetes-induced increase in MAP was also attenuated in patch (82.9 μg/kg)-treated rats. Patch treatment resulted in a decreased heart weight: body weight ratio, as well as reductions in cardiotropin-1, TNF-α, and hsCRP concentrations.. Application of the pectin-insulin patch protects against the debilitating cardiovascular effects associated with conventional diabetes treatment. This suggests that the pectin-insulin patch may provide an effective alternative therapeutic approach to the commonly used subcutaneous insulin injections in the management of diabetes.

Topics: Animals; Blood Glucose; Blood Pressure; C-Reactive Protein; Cardiotonic Agents; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Insulin; Lipids; Male; Pectins; Rats, Sprague-Dawley; Transdermal Patch; Tumor Necrosis Factor-alpha

Gut microbiota (GM) and diet both appear to be important in the pathogenesis of type 1 diabetes. Fermentable fibres (FFs), of which there is an ample supply in natural, diabetes-promoting diets, are used by GM as a source of energy. Our aim was to determine whether FFs modify GM and diabetes incidence in the NOD mouse.. Female NOD mice were weaned to a semisynthetic diet and the effects of FF supplementation on diabetes incidence and insulitis were evaluated. Real-time quantitative PCR was employed to determine the effects imposed to gene transcripts in the colon and lymph nodes. Changes to GM were analysed by next-generation sequencing.. NOD mice fed semisynthetic diets free from FFs were largely protected from diabetes while semisynthetic diets supplemented with the FFs pectin and xylan (PX) resulted in higher diabetes incidence. Semisynthetic diet free from FFs altered GM composition significantly; addition of PX changed the composition of the GM towards that found in natural-diet-fed mice and increased production of FF-derived short-chain fatty acid metabolites in the colon. The highly diabetogenic natural diet was associated with expression of proinflammatory and stress-related genes in the colon, while the semisynthetic diet free from FFs promoted Il4, Il22, Tgfβ and Foxp3 transcripts in the colon and/or pancreatic lymph node. PX in the same diet counteracted these effects and promoted stress-related IL-18 activation in gut epithelial cells. 16S RNA sequencing revealed each diet to give rise to its particular GM composition, with different Firmicutes to Bacteroidetes ratios, and enrichment of mucin-degrading Ruminococcaceae following diabetes-protective FF-free diet.. FFs condition microbiota, affect colon homeostasis and are important components of natural, diabetes-promoting diets in NOD mice.

Topics: Animals; Colon; Diabetes Mellitus, Type 1; Female; Gastrointestinal Tract; Hepatocyte Nuclear Factor 3-gamma; Interleukin-18; Interleukin-22; Interleukin-4; Interleukins; Lymph Nodes; Mice; Mice, Inbred NOD; Microbiota; Pectins; Transforming Growth Factor beta; Xylans

The efficacy of a moderate amount (7 grams) of apple pectin in diminishing post-prandial insulin needs in insulin dependent diabetics (IDD) has been tested using an artificial pancreas in a sequential analysis. With this method, only four patients who served as their own control, showed significant reductions in insulin requirement of 3 Iu with pectin after a 60 g carbohydrate mixed meal. The use of pectin cut by 35 per cent the post prandial insulin demand. The patients judged the treatment as acceptable. More prolonged use in IDD is advisable.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 1; Eating; Female; Humans; Insulin; Insulin Infusion Systems; Kinetics; Male; Middle Aged; Pectins