Posts Tagged ‘Glucose’

Responses of Gut Microbiota and Glucose and Lipid Metabolism to Prebiotics in Genetic Obese and Diet-Induced Leptin-Resistant Mice

September 21st, 2011 admin

OBJECTIVE

To investigate deep and comprehensive analysis of gut microbial communities and biological parameters after prebiotic administration in obese and diabetic mice.

RESEARCH DESIGN AND METHODS

Genetic (ob/ob) or diet-induced obese and diabetic mice were chronically fed with prebiotic-enriched diet or with a normal chow diet. Extensive gut microbiota analyses, including quantitative PCR, pyrosequencing of the 16S rRNA, and phylogenetic microarrays, were performed in ob/ob mice. The impact of gut microbiota modulation on leptin sensitivity was investigated in diet-induced leptin-resistant mice. Metabolic parameters, gene expression, glucose homeostasis, and enteroendocrine-related L-cell function were documented in both models.

RESULTS

In ob/ob mice, prebiotic feeding decreased Firmicutes and increased Bacteroidetes phyla, but also changed 102 distinct taxa, 16 of which displayed a >10-fold change in abundance. In addition, prebiotics improved glucose tolerance, increased L-cell number and associated parameters (intestinal proglucagon mRNA expression and plasma glucagon-like peptide-1 levels), and reduced fat-mass development, oxidative stress, and low-grade inflammation. In high fat–fed mice, prebiotic treatment improved leptin sensitivity as well as metabolic parameters.

CONCLUSIONS

We conclude that specific gut microbiota modulation improves glucose homeostasis, leptin sensitivity, and target enteroendocrine cell activity in obese and diabetic mice. By profiling the gut microbiota, we identified a catalog of putative bacterial targets that may affect host metabolism in obesity and diabetes.


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Reduction in Reactive Oxygen Species Production by Mitochondria From Elderly Subjects With Normal and Impaired Glucose Tolerance

June 23rd, 2011 admin

OBJECTIVE

Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in subjects with normal glucose tolerance [NGT]) impairs mitochondrial function and how this relates to ROS generation, whether older subjects with IGT have a further worsening of mitochondrial function (lower ATP production and elevated ROS generation), and whether exercise reverses age-related changes in mitochondrial function.


RESEARCH DESIGN AND METHODS

Mitochondrial ATP and ROS production were measured in muscle from younger individuals with NGT, older individuals with NGT, and older individuals with IGT. Measurements were performed before and after 16 weeks of aerobic exercise.


RESULTS

ATP synthesis was lower in older subjects with NGT and older subjects with IGT versus younger subjects. Notably, mitochondria from older subjects (with NGT and IGT) displayed reduced ROS production versus the younger group. ATP and ROS production were similar between older groups. Exercise increased ATP synthesis in the three groups. Mitochondrial ROS production also increased after training. Proteomic analysis revealed downregulation of several electron transport chain proteins with aging, and this was reversed by exercise.


CONCLUSIONS

Old mitochondria from subjects with NGT and IGT display mitochondrial dysfunction as manifested by reduced ATP production but not with respect to increased ROS production. When adjusted to age, the development of IGT in elderly individuals does not involve changes in mitochondrial ATP and ROS production. Lastly, exercise reverses the mitochondrial phenotype (proteome and function) of old mitochondria.

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Fasting-Induced Protein Phosphatase 1 Regulatory Subunit Contributes to Postprandial Blood Glucose Homeostasis via Regulation on Hepatic Glycogenesis

April 14th, 2011 admin

OBJECTIVE

Most animals experience fasting–feeding cycles throughout their lives. It is well known that the liver plays a central role in regulating glycogen metabolism. However, how hepatic glycogenesis is coordinated with the fasting–feeding cycle to control postprandial glucose homeostasis remains largely unknown. This study determines the molecular mechanism underlying the coupling of hepatic glycogenesis with the fasting–feeding cycle.


RESEARCH DESIGN AND METHODS

Through a series of molecular, cellular, and animal studies, we investigated how PPP1R3G, a glycogen-targeting regulatory subunit of protein phosphatase 1 (PP1), is implicated in regulating hepatic glycogenesis and glucose homeostasis in a manner tightly orchestrated with the fasting–feeding cycle.


RESULTS

PPP1R3G in the liver is upregulated during fasting and downregulated after feeding. PPP1R3G associates with glycogen pellet, interacts with the catalytic subunit of PP1, and regulates glycogen synthase (GS) activity. Fasting glucose level is reduced when PPP1R3G is overexpressed in the liver. Hepatic knockdown of PPP1R3G reduces postprandial elevation of GS activity, decreases postprandial accumulation of liver glycogen, and decelerates postprandial clearance of blood glucose. Other glycogen-targeting regulatory subunits of PP1, such as PPP1R3B, PPP1R3C, and PPP1R3D, are downregulated by fasting and increased by feeding in the liver.


CONCLUSIONS

We propose that the opposite expression pattern of PPP1R3G versus other PP1 regulatory subunits comprise an intricate regulatory machinery to control hepatic glycogenesis during the fasting–feeding cycle. Because of its unique expression pattern, PPP1R3G plays a major role to control postprandial glucose homeostasis during the fasting–feeding transition via its regulation on liver glycogenesis.

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Association of a fasting glucose genetic risk score with subclinical atherosclerosis: The Atherosclerosis Risk in Communities (ARIC) Study

December 20th, 2010 admin

AbstractObjective:

Elevated fasting glucose level is associated with increased carotid intima-media thickness (IMT), a measure of subclinical atherosclerosis. It is unclear if this association is causal. Using the principal of Mendelian randomization we sought to explore the causal association between circulating glucose and IMT by examining the association of a genetic risk score with IMT.


Research Design and Methods:

The sample was drawn from the ARIC study and included7260 non-diabetic Caucasian individuals with IMT measurements and relevant genotyping. Components of the fasting glucose genetic risk score (FGGRS) were selected from a fasting glucose GWAS in ARIC. The score was created by combining five SNPs (rs780094 [GCKR], rs560887 [G6PC2], rs4607517 [GCK], rs13266634 [SLC30A8], and rs10830963 [MTNR1B]) and weighting each SNP by its strength of association with fasting glucose. IMT was measured through bilateral carotid ultrasound. Mean IMT was regressed on the FGGRS and on the component SNPs, individually.


Results:

The FGGRS was significantly associated (p = .009) with mean IMT The difference in IMT predicted by a 1 SD increment in the FGGRS, (0.0048 mm), was not clinically relevant but was larger than would have been predicted based on observed associations between the FFGRS, fasting glucose, and IMT. Additional adjustment for baseline measured glucose in regression models attenuated the association by about one third.


Conclusions:

The significant association of the fasting glucose genetic risk score with IMT suggests a possible a causal association of elevated fasting glucose with atherosclerosis although it may be that these loci influence IMT through non-glucose pathways.



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Congenital hyperinsulinism and glucose hypersensitivity in homozygous and heterozygous carriers of Kir6.2 (KCNJ11) mutation V290M mutation: KATP channel inactivation mechanism and clinical management

December 5th, 2010 admin

AbstractObjective:

The ATP-sensitive K+-channel (KATP) controls insulin secretion from the islet. Gain- or loss-of-function mutations in channel subunits underlie human neonatal diabetes mellitus (NDM) and congenital hyperinsulinism (HI), respectively. In this study we sought to identify the mechanistic basis of KATP-induced HI in two probands, and characterize the clinical course.


Research Design and Methods:

We analyzed HI in two probands and characterized the course of clinical treatment in each, as well as properties of mutant KATP channels expressed in COSm6 cells using Rb efflux and patch-clamp methods.


Results:

We identified mutation V290M in the pore-forming Kir6.2 subunit in each proband. In vitro expression in COSm6 cells supports the mutation resulting in an inactivating phenotype, which leads to significantly reduced activity in intact cells when expressed homomerically, and to a lesser extent when expressed heteromerically with WT subunits. In one heterozygous proband, fluoro-DOPA scan revealed a causal focal lesion, indicating uniparental disomy with loss of heterozygosity. In a second family, the proband, homozygous for the mutation, was diagnosed with severe diazoxide-unresponsive hypersinsulinism at 2 weeks of age. The patient continues to be treated successfully with octreotide and amlodipine. The parents and a male sibling are heterozygous carriers without overt clinical HI. Interestingly, both the mother and the sibling exhibit evidence of abnormally enhanced glucose tolerance.


Conclusions:

V290M results in inactivating KATP channels that underlies HI. Homozygous individuals may be managed medically, without pancreatectomy. Heterozygous carriers also show evidence of enhanced glucose sensitivity, consistent with incomplete loss of KATP channel activity.



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Blood Glucose Monitoring

October 28th, 2010 admin

How blood glucose monitoring can control diabetes. Watch this and more health videos at: www.answerstv.com

Pavel Fort MD Ped Endo
Video Rating: 5 / 5

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