scholarly journals Enhanced insulin sensitivity of gene-targeted mice lacking functional KCNQ1

2009 ◽  
Vol 296 (6) ◽  
pp. R1695-R1701 ◽  
Author(s):  
Krishna M. Boini ◽  
Dirk Graf ◽  
Anita M. Hennige ◽  
Saisudha Koka ◽  
Daniela S. Kempe ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Peak Plasma ◽  
Plasma Glucose Concentration ◽  
Α Subunit ◽  
Glucose Injection ◽  
Regulation Of Metabolism

The pore-forming K+-channel α-subunit KCNQ1 is expressed in a wide variety of tissues including heart, skeletal muscle, liver, and epithelia. Most recent evidence revealed an association of the KCNQ1 gene with the susceptibility to type 2 diabetes. KCNQ1 participates in the regulation of cell volume, which is, in turn, critically important for the regulation of metabolism by insulin. The present study explored the influence of KCNQ1 on insulin-induced cellular K+ uptake and glucose metabolism. Insulin (100 nM)-induced K+ uptake was determined in isolated perfused livers from KCNQ1-deficient mice ( kcnq1−/−) and their wild-type littermates ( kcnq1+/+). Moreover, plasma glucose and insulin levels, intraperitoneal glucose (3 g/kg) tolerance, insulin (0.15 U/kg)-induced hypoglycemia, and peripheral uptake of radiolabeled 3H-deoxy-glucose were determined in both genotypes. Insulin-stimulated hepatocellular K+ uptake was significantly more sustained in isolated perfused livers from kcnq1−/− mice than from kcnq1+/+mice. The decline of plasma glucose concentration following an intraperitoneal injection of insulin was again significantly more sustained in kcnq1−/− than in kcnq1+/+ mice. Both fasted and nonfasted plasma glucose and insulin concentrations were significantly lower in kcnq1−/− than in kcnq1+/+mice. Following an intraperitoneal glucose injection, the peak plasma glucose concentration was significantly lower in kcnq1−/− than in kcnq1+/+mice. Uptake of 3H-deoxy-glucose into skeletal muscle, liver, kidney and lung tissue was significantly higher in kcnq1−/− than in kcnq1+/+mice. In conclusion, KCNQ1 counteracts the stimulation of cellular K+ uptake by insulin and thereby influences K+-dependent insulin signaling on glucose metabolism. The observations indicate that KCNQ1 is a novel molecule affecting insulin sensitivity of glucose metabolism.

scholarly journals 1-Hour OGTT Plasma Glucose as a Marker of Progressive Deterioration of Insulin Secretion and Action in Pregnant Women

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Alessandra Ghio ◽  
Giuseppe Seghieri ◽  
Cristina Lencioni ◽  
Roberto Anichini ◽  
Alessandra Bertolotto ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Pregnant Women ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Insulin Action ◽  
Progressive Increase ◽  
Plasma Glucose Concentration ◽  
Linear Manner

Considering old GDM diagnostic criteria, alterations in insulin secretion and action are present in women with GDM as well as in women with one abnormal value (OAV) during OGTT. Our aim is to assess if changes in insulin action and secretion during pregnancy are related to 1-hour plasma glucose concentration during OGTT. We evaluated 3 h/100 g OGTT in 4,053 pregnant women, dividing our population on the basis of 20 mg/dL increment of plasma glucose concentration at 1 h OGTT generating 5 groups (<120 mg/dL,n=661; 120–139 mg/dL,n=710; 140–159 mg/dL,n=912; 160–179 mg/dL,n=885; and ≥180 mg/dL,n=996). We calculated incremental area under glucose (AUCgluc) and insulin curves (AUCins), indexes of insulin secretion (HOMA-B), and insulin sensitivity (HOMA-R), AUCins/AUCgluc. AUCglucand AUCinsprogressively increased according to 1-hour plasma glucose concentrations (bothP<0.0001for trend). HOMA-B progressively declined (P<0.001), and HOMA-R progressively increased across the five groups. AUCins/AUCglucdecreased in a linear manner across the 5 groups (P<0.001). Analysing the groups with 1-hour value <180 mg/dL, defects in insulin secretion (HOMA-B: −29.7%) and sensitivity (HOMA-R: +15%) indexes were still apparent (allP<0.001). Progressive increase in 1-hour OGTT is associated with deterioration of glucose tolerance and alterations in indexes of insulin action and secretion.

FURTHER STUDIES ON THE EFFECT OF OCTANOATE ON GLUCOSE METABOLISM IN DOGS

1967 ◽  
Vol 45 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Shafeek S. Sanbar ◽  
John R. Evans ◽  
Boniface Lin ◽  
Geza Hetenyi Jr.
Keyword(s):  
Glucose Metabolism ◽  
Intravenous Administration ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Peripheral Blood ◽  
Plasma Insulin ◽  
Plasma Glucose Concentration ◽  
Intravenous Glucose ◽  
K Value ◽  
Healthy Dogs

Studies were carried out in anesthetized dogs to elucidate the mechanism of action of octanoate on glucose metabolism.Octanoate infusion in intact healthy dogs significantly decreased plasma glucose concentration, and in four out of seven dogs it raised plasma insulin concentration in peripheral blood. In contrast, intravenous administration of octanoate in four totally pancreatectomized dogs produced only small changes in plasma glucose concentration. These data suggest that the hypoglycemic action of octanoate may be mediated by increased secretion of insulin.The mean k value ([Formula: see text] of plasma glucose concentration) of intravenous glucose tolerance tests was significantly higher (2.38/minute) in healthy dogs that received an infusion of octanoate than in dogs that did not (1.2/minute). Octanoate also produced in healthy dogs greater increases in plasma insulin concentrations of peripheral blood during the tolerance tests. Furthermore, when delivered during a continuous intravenous administration of glucose (about 8 mg/kg per minute), octanoate infusion had no effect on either plasma glucose concentration or the rate of disappearance of glucose-U-14C from plasma to tissues. These findings indicate that octanoate does not impair glucose utilization in healthy dogs but actually improves tolerance of an intravenous glucose load, probably by stimulating greater release of insulin. These findings in vivo are discussed in the light of opposite effects of octanoate in vitro, to be described elsewhere, on glucose metabolism in the isolated heart and fat pad of rats.

Betacellulin improves glucose metabolism by promoting conversion of intraislet precursor cells to β-cells in streptozotocin-treated mice

2003 ◽  
Vol 285 (3) ◽  
pp. E577-E583 ◽  
Author(s):  
Lei Li ◽  
Masaharu Seno ◽  
Hidenori Yamada ◽  
Itaru Kojima
Keyword(s):  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Experimental Diabetes ◽  
Islet Cells ◽  
Plasma Glucose Concentration ◽  
High Dose ◽  
Β Cells ◽  
Plasma Insulin Concentration ◽  
Severe Diabetes

Betacellulin (BTC) induces differentiation of pancreatic β-cells and promotes regeneration of β-cells in experimental diabetes. The present study was conducted to determine if BTC improved glucose metabolism in severe diabetes induced by a high dose of streptozotocin (STZ) in mice. Male ICR mice were injected with 200 μg/g ip STZ, and various doses of BTC were administered daily for 14 days. The plasma glucose concentration increased to a level of >500 mg/dl in STZ-injected mice. BTC (0.2 μg/g) significantly reduced the plasma glucose concentration, but a higher concentration was ineffective. The effect of BTC was marked by day 4 but became smaller on day 6 or later. The plasma insulin concentration and the insulin content were significantly higher in mice treated with 0.1 and 0.2 μg/g BTC. BTC treatment significantly increased the number of β-cells in each islet as well as the number of insulin-positive islets. Within islets, the numbers of 5-bromo-2-deoxyuridine/somatostatin-positive cells and pancreatic duodenal homeobox-1/somatostatin-positive cells were significantly increased by BTC. These results indicate that BTC improved hyperglycemia induced by a high dose of STZ by promoting neoformation of β-cells, mainly from somatostatin-positive islet cells.

scholarly journals Anti-inflammatory salicylate treatment alters the metabolic adaptations to lactation in dairy cattle

2013 ◽  
Vol 305 (2) ◽  
pp. R110-R117 ◽  
Author(s):  
Jaymelynn K. Farney ◽  
Laman K. Mamedova ◽  
Johann F. Coetzee ◽  
Butch KuKanich ◽  
Lorraine M. Sordillo ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Plasma Glucose ◽  
Glucose Concentration ◽  
Glucose Utilization ◽  
Physiological State ◽  
Plasma Glucose Concentration ◽  
Utilization Rate ◽  
Peripheral Tissues ◽  
Tnf Α ◽  
Anti Inflammatory

Adapting to the lactating state requires metabolic adjustments in multiple tissues, especially in the dairy cow, which must meet glucose demands that can exceed 5 kg/day in the face of negligible gastrointestinal glucose absorption. These challenges are met through the process of homeorhesis, the alteration of metabolic setpoints to adapt to a shift in physiological state. To investigate the role of inflammation-associated pathways in these homeorhetic adaptations, we treated cows with the nonsteroidal anti-inflammatory drug sodium salicylate (SS) for the first 7 days of lactation. Administration of SS decreased liver TNF-α mRNA and marginally decreased plasma TNF-α concentration, but plasma eicosanoids and liver NF-κB activity were unaltered during treatment. Despite the mild impact on these inflammatory markers, SS clearly altered metabolic function. Plasma glucose concentration was decreased by SS, but this was not explained by a shift in hepatic gluconeogenic gene expression or by altered milk lactose secretion. Insulin concentrations decreased in SS-treated cows on day 7 compared with controls, which was consistent with the decline in plasma glucose concentration. The revised quantitative insulin sensitivity check index (RQUICKI) was then used to assess whether altered insulin sensitivity may have influenced glucose utilization rate with SS. The RQUICKI estimate of insulin sensitivity was significantly elevated by SS on day 7, coincident with the decline in plasma glucose concentration. Salicylate prevented postpartum insulin resistance, likely causing excessive glucose utilization in peripheral tissues and hypoglycemia. These results represent the first evidence that inflammation-associated pathways are involved in homeorhetic adaptations to lactation.

scholarly journals Direct Chemical Measurement of the λ of the Lumped Constant of the [14C]Deoxyglucose Method in Rat Brain: Effects of Arterial Plasma Glucose Level on the Distribution Spaces of [14C]Deoxyglucose and Glucose and on λ

1989 ◽  
Vol 9 (3) ◽  
pp. 304-314 ◽  
Author(s):  
Kentaro Mori ◽  
Nancy Cruz ◽  
Gerald Dienel ◽  
Thomas Nelson ◽  
Louis Sokoloff
Keyword(s):  
Plasma Glucose ◽  
Glucose Concentration ◽  
Severe Hypoglycemia ◽  
Plasma Glucose Concentration ◽  
Operational Equation ◽  
Chemical Measurements ◽  
Lumped Constant ◽  
Dg Method ◽  
Arterial Plasma ◽  
Distribution Spaces

The lumped constant in the operational equation of the 2-[14C]deoxyglucose (DG) method contains the factor λ that represents the ratio of the steady-state tissue distribution spaces for [14C]DG and glucose. The lumped constant has been shown to vary with arterial plasma glucose concentration. Predictions based mainly on theoretical grounds have suggested that disproportionate changes in the distribution spaces for [14C]DG and glucose and in the value of λ are responsible for these variations in the lumped constant. The influence of arterial plasma glucose concentration on the distribution spaces for DG and glucose and on λ were, therefore, determined in the present studies by direct chemical measurements. The brain was maintained in steady states of delivery and metabolism of DG and glucose by programmed intravenous infusions of both hexoses designed to produce and maintain constant arterial concentrations. Hexose concentrations were assayed in acid extracts of arterial plasma and freeze-blown brain. Graded hyperglycemia up to 28 m M produced progressive decreases in the distribution spaces of both hexoses from their normoglycemic values (e.g., ∼ – 20% for glucose and – 50% for DG at 28 m M). In contrast, graded hypoglycemia progressively reduced the distribution space for glucose and increased the space for [14C]DG. The values for λ were comparatively stable in normoglycemic and hyperglycemic conditions but rose sharply (e.g., as much as 9–10-fold at 2 m M) in severe hypoglycemia.

scholarly journals Comparative Study of Fasting Plasma Glucose Concentration and Glucose Challenge Test for Screening Gestational Diabetes Mellitus

2014 ◽  
Vol 6 (2) ◽  
pp. 75-78
Author(s):  
Sujaya Sham ◽  
B Poornima R Bhat ◽  
Aruna Kamath
Keyword(s):  
Diabetes Mellitus ◽  
Plasma Glucose ◽  
Fasting Plasma Glucose ◽  
Glucose Concentration ◽  
Challenge Test ◽  
Plasma Glucose Concentration ◽  
Fasting Plasma ◽  
Glucose Challenge Test ◽  
Glucose Challenge ◽  
Fasting Plasma Glucose Concentration

ABSTRACT Background To compare the sensitivity and specificity of fasting plasma glucose (FPG) with that of standard glucose challenge test (GCT). Materials and methods Eighty-nine eligible pregnant women underwent GCT between 24th and 28th gestational week, followed by a diagnostic 3 hours 100 gm oral glucose tolerance test within 1 week. Out patient clinic in Father Muller Medical College Hospital, Mangalore. Data was analyzed for significance by chi-square test. Results Fasting plasma glucose concentration at a threshold value of 90 mg/dl and GCT at recommended standard threshold of 140 mg/dl yielded sensitivities of 66.7% and 100% respectively and specificities of 87.3% and 46.5% respectively. Reducing the threshold value of FPG to 80 mg/dl increased the sensitivity of test to 91.7% with specificity of 54.9% which was comparable to standard GCT, in our study. Conclusion Measuring FPG concentration using a cut-off of. 80 mg/dl is an easier, tolerable and more cost effective procedure than GCT for detecting more severe cases of GDM, i.e. the diabetes mellitus group. In resource poor settings with population belonging to average risk or high risk category, FPG at a cut-off of 90 mg/dl can be used to screen GDM. How to cite this article Sham S, Bhat BPR, Kamath A. Comparative Study of Fasting Plasma Glucose Concentration and Glucose Challenge Test for Screening Gestational Diabetes Mellitus. J South Asian Feder Obst Gynae 2014;6(2):75-78.

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