Diabesity (E-Journal)
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Fat and skinny bacteria?
Get PDFDue to the increased availability of high-throughput DNA-sequencing technologies and quantitative PCR, investigators have flooded the scientific literature with reports describing the composition of different gastrointestinal microbiotas. With the use of gnotobiotic isolators housing axenic animals, i.e. germ- or microbiota-free animals, investigators have also undertaken more hypothesis-driven research addressing putative roles for the microbiota in host health. Possibly inspired by the patent spread and pathogenesis of obesity and metabolic syndrome, in combination with the observation that a commonly used strain of germ-free laboratory mice are more resistant to obesity than their conventional counterparts a major focus of much of this work has considered the relationship between the microbiota of the host and the susceptibility of the host to obesity. Additionally, compared to many existing and theoretic therapeutics to counter the obesity pandemic, the microbiota is potentially a more practical target. I attempt to very briefly summarize, for nonprofessionals of microbiome study, the composition of the microbiota as it relates to obesity in humans. This is intended to provide the reader with sources for finding further information, including primary research that has contributed to our knowledge and more comprehensive reviews on the relevant topics mentioned
Effect of Caesalpinia pulcherrima (L.) Sw. seeds on serum glucose and other metabolic parameters of normal and alloxan - induced diabetic rats
Get PDFOral administration of the ethanol extract of Caesalpinia pulcherrima seeds (CP - 250 and 500 mg/kg) caused significant fall in blood glucose levels even at 2½ h after a single dose of treatment in normal fasted and glucose loaded Wistar rats. At 250 mg/kg dose level, CP completely prevented the elevation of blood glucose caused by oral glucose feeding. In alloxan diabetic rats, CP was able to lower the blood glucose level to around 132 mg / 100 ml from 10th day and thereafter. The biochemical findings were supported by histopathological studies of liver, kidney and pancreas of control and treated rats. CP was able to increase catalase levels of diabetic rats. Reduced levels of serum protein and elevated levels of serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase(SGPT), alkaline phosphatase(ALP), cholesterol, triglycerides, creatinine and uric acid were almost normalised in CP treated diabetic rats. CP was also able to reduce in vitro lipid peroxidation in rat liver microsomes and inhibit 1- diphenyl – 2-picryl hydrazyl (DPPH) induced free radicals significantly
Effect of Cyclodextrin Garcinol Complex on Pressure Overload- Induced Cardiotoxicity and Cardiac Hypertrophy by Aortic Stenosis in Rats
Get PDFBackground: Garcinol is a polyisoprenylated benzophenone derived from rinds of fruit of Garcinia species namely Garciniaindica (common name ‘Kokum’) and Garcinia cambogia (common name ‘Gombogee’). Garcinol is not stable and has poor bioavailability which can be improved by complexing garcinol with cyclodextrin (cyclodextringarcinol complex). Objective: The objective of the present study was to investigate effect of cyclodextrin-garcinol complex (20 mg/kg/) on pressure overloadinduced cardiotoxicity and cardiac hypertrophy by aortic stenosis in rats. Methods: Male Wistar rats (250-300g) were divided into following four groups such as: control, sham, stenosis and cyclodextrin-garcinol complex. Daily body weights were recorded. Cyclodextrin-garcinol complex (20 mg/kg/day) in distilled water, was administered orally to rats daily for 18 days and then the animals underwent surgery with aortic binding, the treatment was continued up to 4-6 weeks. Haemodynamic changes and electrocardiogram (ECG) were recorded in anaesthetized rats. Results: Pressure overload induced by arotic stenosis in rat resulted in significant myocardial hypertrophy and decreased endogenous antioxidants when compared with the control and sham group animals. Cyclodextrin-garcinol complex (20 mg/kg) showed significant cardioprotective activity by lowering the myocardial hypertrophy, level of lipid peroxidation (MDA content) as well as elevated the level of GSH. The results suggest pre-treatment of cyclodextrin-garcinol complex (20 mg/kg), may offer potential benefits in the management of cardiotoxicity and cardiac hypertrophy. Conclusion: It is concluded that cyclodextrin-garcinol complex (20 mg/kg) protected the haemodynamics of stenosized heart of rats by reduction of lipid peroxidation and preservation of endogenous antioxidants in rat heart
A potential role for mTORC1/2 in β2 adrenergic regulation of skeletal muscle glucose oxidation in models of intrauterine growth restriction.
Get PDFThe epidemic of intrauterine growth restriction (IUGR) continues to be a leading cause of perinatal morbidity and mortality throughout the world. This condition has been linked to the development of metabolic health problems such as obesity, hypertension, glucose intolerance, and type 2 diabetes at all ages. Previous studies have demonstrated that IUGR fetal adaptations impair proper glucose homeostasis in part via changes in insulin responsiveness in key tissues including skeletal muscle and liver, and that these deficits persists into adulthood. Many components of insulin signaling pathways associated with glucose metabolic regulation have been evaluated in IUGR tissues for adaptive changes. Among these are mammalian target of rapamycin complexes 1 and 2 (mTORC1/2) and their associated pathways, which function in mitochondrial control and maintenance. However, recent findings demonstrate that β2 adrenoceptors (β2AR) appear to activate an insulin-independent pathway or pathways that modify glucose metabolism via mTORC1/2 complexes. These findings represent a novel potential target for interventions that could improve the treatment and prevention of IUGR-induced metabolic disorders. This review will focus on mechanistic components of β2AR-mTORC1/2 signaling as well as their role in regulating glucose oxidative metabolism within skeletal muscle
Modulating Weight Loss and Regain through Exercise and Dietary Protein
Get PDFEfficacious weight loss which reduces risk of mortality requires both significant initial weight loss and prevention of weight regain. Performing either aerobic or resistance exercise and elevating protein intake during caloric restriction (CR) preserves—and may increase—lean mass (LM), leading to targeted loss of fat mass. To maximize the LM retention stimulus achieved by consuming high-protein diets, gross and acute dosage, distribution and source of protein should all be optimized. Maintenance of LM during weight loss may improve satiety during CR and aids in the prevention of weight regain by blunting the post-CR hyperphagic response which causes overcompensation of fat mass regain known as the fat overshoot phenomenon. Overall, the combination of exercise and high protein diet promotes efficacious weight loss through preservation of LM, which resists weight regain
PCSK9 inhibitors – Clinical viability and practical considerations
Get PDFThe U.S. Food and Drug Administration and other regulatory bodies recently approved Praluent (alirocumab) and Repatha (evolocumab) for patients with hereditary forms of high cholesterol and those with cardiovascular disease. These drugs belong to a potent new class of injectable LDL-lowering drugs known as PCSK9 inhibitors. Repatha was approved to treat patients with heterozygous familial hypercholesterolemia (HeFH) and patients with the rarer homozygous (HoFH) form of the disease. It was also approved for patients with cardiovascular disease including heart attack or stroke, who require additional cholesterol lowering. The scope of the approval was similar to the approval given to the Regeneron drug, Praluent (alirocumab), which was approved for patients with cardiovascular disease and those with HeFH
The potential of mesenchymal stem cells in diabetes mellitus
Get PDFWhile exogenous insulin and oral hypoglycemic agents are helpful in controlling the blood glucose level in diabetic patients, these agents are occasionally resulted in hypoglycemic coma. Considering the epidemiology of the diabetic population in the world, we require a better therapeutic strategy like expanding the existing beta- cells within the body or by supplying exogenous insulin-producing stem cells. A variety of stem cells have been tested for the treatment of type 1 and type 2 diabetes mellitus, and among them, mesenchymal stem cells (MSCs) are widely used because of their immunomodulatory and low-immunogenic characteristics. So far, eight clinical trials have been completed using MSCs for the treatment of diabetes mellitus. Although the results of the currently available clinical trials are encouraging, i.e. in improving function of the pancreatic beta cells and in controlling the complications associated with diabetes, we
require larger, randomized, and double-blinded studies, with a longer duration of follow-up, to validate the findings obtained
Hyperinsulinemia: Best management practice
Get PDFChronic hyperinsulinemia associated with insulin resistance is directly and indirectly associated with many metabolic disorders that contribute to significant morbidity and mortality. Because hyperinsulinemia is not widely recognised as an independent health risk, there are few studies that assess management strategies. Medication management may not address the multiple issues associated with hyperinsulinemia. Lifestyle management includes physical activity, especially high intensity interval training, and dietary management. Reducing carbohydrate quantity and increasing nutrient density are discussed with carbohydrate-restricted and Mediterranean diets conferring additional benefits to a low-fat diet. Physical activity and dietary management provide the foundation for hyperinsulinemia management and may work synergistically. Of these principles, a combination of resistance and high intensity interval training, and carbohydrate restriction provide the two most effective frontline management strategies for managing hyperinsulinemia
SGLT-2 inhibitors – are they to stay?
Get PDFSodium-glucose co-transporter 2 (SGLT2) inhibitors are a newer class of Type 2 diabetes medications. The drugs are rapidly growing in popularity. In the period between October 2014
and September 2015, doctors wrote 1.5 million prescriptions for Invokana or Farxiga (dapagliflozin), according to the FDA. They also come in extended formulas and in formulas combined with metformin. These drugs work by preventing the kidneys from reabsorbing sugar and releasing it into the blood. But, what makes these medications so effective, could also contribute to a number of side effects. Beginning in December 2015, the FDA released a number of warnings linking these drugs to a number of side effects, some can be fatal. These range from common ones like yeast infections to more dangerous, rare problems like a link to increased
bladder cancer risk and diabetic ketoacidosi
Effect of cyclodextrin garcinol complex on isoproterenol-induced cardiotoxicity and cardiac hypertrophy in rats
Get PDFBackground: Garcinol is a polyisoprenylated benzophenone derivative present in the fruit rinds of Garcinia species namely Garcinia indica (common name 'Kokum') and Garcinia cambogia (common name 'Gombogee'). It appears to be involved in the regulation of oxidative stress and antioxidant capacity of heart tissue when the heart is subjected to oxidative stress in various pathogenic conditions/ chemical agent. But garcinol is associated with severe limitation of instability and poor bioavailability which can be improved complexing cyclodextrin with garcinol (garcinol complex). Objective: The objective of the present study was to investigate effect of cyclodextrin with garcinol complex (20 mg/kg), on Iso induced cardiotoxicity and cardiac hypertrophy in rats.Methods: Male Wistar rats (250-300g) were divided into following 4 groups of six animals each. Group 1 was control (distilled water 2 ml/kg/day orally for 18 days and water for injection by i.p. from day 9 to day 18), group 2 was cyclodextrin (cyclodextrin 2 ml/kg/day orally for 18 days and water for injection by i.p. from day 9 to day 18), group 3 Iso (distilled water 2 ml/kg/day orally for 18 days and isoproterenol 1 mg/kg by i.p. from day 9 to day 18), group 4 garcinol complex (20 mg/kg/day orally for 18 days and isoproterenol 1 mg/kg by i.p. from day 9 to day 18). After 24 hrs of last dose of isoproterenol, electrocardiogram (ECG) and heart rate were recorded in anaesthetized rats. The animals were sacrificed by overdose of ether. The hearts of animals were isolated for measurement of reduced glutathione (GSH) and lipid peroxidation (MDA). Results: Isoproterenol treated rats showed significant myocardial hypertrophy, decreased endogenous antioxidants when compared with the control group animals. The garcinol complex (20 mg/kg) treatment for 18 days showed significant cardioprotective activity by lowering the myocardial hypertrophy, level of lipid peroxidation (MDA content) as well as elevated the level of GSH. The results suggest pre-treatment of garcinol complex (20 mg/kg), may offer potential benefits in the management of cardiotoxicity and cardiac hypertrophy. Conclusion: It is thus concluded that Garcinol Complex (20 mg/kg) administration offered significant protection against isoproterenol induced cardiotoxicity and cardiac hypertrophy as well as decreased myocardial injury by preservation of endogenous antioxidants and reduction of lipid peroxidation in rat heart