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Increase in Endogenous Glucose Production With SGLT2 Inhibition Is Unchanged by Renal Denervation and Correlates Strongly With the Increase in Urinary Glucose Excretion.
Solis-Herrera, C, Daniele, G, Alatrach, M, Agyin, C, Triplitt, C, Adams, J, Patel, R, Gastaldelli, A, Honka, H, Chen, X, et al
Diabetes care. 2020;(5):1065-1069
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Abstract
OBJECTIVE Sodium-glucose cotransporter 2 (SGLT2) inhibition causes an increase in endogenous glucose production (EGP). However, the mechanisms are unclear. We studied the effect of SGLT2 inhibitors on EGP in subjects with type 2 diabetes (T2D) and without diabetes (non-DM) in kidney transplant recipients with renal denervation. RESEARCH DESIGN AND METHODS Fourteen subjects who received a renal transplant (six with T2D [A1C 7.2 ± 0.1%] and eight non-DM [A1C 5.6 ± 0.1%) underwent measurement of EGP with [3-3H]glucose infusion following dapagliflozin (DAPA) 10 mg or placebo. Plasma glucose, insulin, C-peptide, glucagon, and titrated glucose-specific activity were measured. RESULTS Following placebo in T2D, fasting plasma glucose (FPG) (143 ± 14 to 124 ± 10 mg/dL; P = 0.02) and fasting plasma insulin (12 ± 2 to 10 ± 1.1 μU/mL; P < 0.05) decreased; plasma glucagon was unchanged, and EGP declined. After DAPA in T2D, FPG (143 ± 15 to 112 ± 9 mg/dL; P = 0.01) and fasting plasma insulin (14 ± 3 to 11 ± 2 μU/mL; P = 0.02) decreased, and plasma glucagon increased (all P < 0.05 vs. placebo). EGP was unchanged from baseline (2.21 ± 0.19 vs. 1.96 ± 0.14 mg/kg/min) in T2D (P < 0.001 vs. placebo). In non-DM following DAPA, FPG and fasting plasma insulin decreased, and plasma glucagon was unchanged. EGP was unchanged from baseline (1.85 ± 0.10 to 1.78 ± 0.10 mg/kg/min) after DAPA, whereas EGP declined significantly with placebo. When the increase in EGP production following DAPA versus placebo was plotted against the difference in urinary glucose excretion (UGE) for all patients, a strong correlation (r = 0.824; P < 0.001) was observed. CONCLUSIONS Renal denervation in patients who received a kidney transplant failed to block the DAPA-mediated stimulation of EGP in both individuals with T2D and non-DM subjects. The DAPA-stimulated rise in EGP is strongly related to the increase in UGE, blunting the decline in FPG.
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Intrinsic peroxidase-like catalytic activity of nitrogen-doped graphene quantum dots and their application in the colorimetric detection of H2O2 and glucose.
Lin, L, Song, X, Chen, Y, Rong, M, Zhao, T, Wang, Y, Jiang, Y, Chen, X
Analytica chimica acta. 2015;:89-95
Abstract
In this paper, the highly intrinsic peroxidase-like catalytic activity of nitrogen-doped graphene quantum dots (N-GQDs) is revealed. This activity was greatly dependent on pH, temperature and H2O2 concentration. The experimental results showed that the stable N-GQDs could be used for the detection of H2O2 and glucose over a wide range of pH and temperature, offering a simple, highly selective and sensitive approach for their colorimetric sensing. The linearity between the analyte concentration and absorption ranged from 20 to 1170 μM for H2O2 and 25 to 375 μM for glucose with a detection limit of 5.3 μM for H2O2 and 16 μM for glucose. This assay was also successfully applied to the detection of glucose concentrations in diluted serum and fruit juice samples.
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Glucose biosensor based on three dimensional ordered macroporous self-doped polyaniline/Prussian blue bicomponent film.
Chen, X, Chen, Z, Tian, R, Yan, W, Yao, C
Analytica chimica acta. 2012;:94-100
Abstract
In this paper, a three dimensional ordered macroporous self-doped polyaniline/Prussian blue (3DOM SPAN/PB) bicomponent film was fabricated via the inverted crystal template technique using step-by-step electrodeposition. In this bicomponent film, PB not only acted as a redox mediator, but also presented increased stability in neutral or weak alkaline solution by the protection of SPAN layer on the top. A novel glucose biosensor was fabricated based on the large active surface area and excellent conductivity possessed by the 3DOM SPAN/PB film. The applying experimental conditions of the glucose biosensor have been optimized. Under the optimal conditions, the biosensor showed a wide linear range over three orders of magnitude in glucose concentrations (from 2 to 1600 μM) and a low detection limit of 0.4 μM. Moreover, the biosensor exhibited short response time, high selectivity and excellent operation stability, which can be applied to detect the blood sugar in real samples without any pretreatment.
4.
Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes.
Boden, G, Chen, X, Capulong, E, Mozzoli, M
Diabetes. 2001;(4):810-6
Abstract
Effects of endogenously derived free fatty acids (FFAs) on rates of gluconeogenesis (GNG) (determined with 2H2O), glycogenolysis (GL), and endogenous glucose production (EGP) were studied in 18 type 2 diabetic patients and in 7 nondiabetic control subjects under three experimental conditions: 1) during an 8-h fast (from 16-24 h after the last meal), when plasma FFA levels increased slowly; 2) during 4 h (from 16-20 h) of nicotinic acid (NA) administration (fasting plus NA), when plasma FFAs decreased acutely; and 3) during 4 h (from 20-24 h) after discontinuation of NA (FFA rebound), when plasma FFAs increased acutely. During fasting, FFAs increased from 636 to 711 micromol/l in type 2 diabetic patients and from 462 to 573 micromol/l in control subjects (P < 0.04), but GNG did not change in diabetic patients (6.9 vs. 6.5 micromol x kg(-1) x min(-1), P > 0.05) or in control subjects (5.1 vs. 5.4 micromol x kg(-1) x min(-1), P > 0.05). During fasting plus NA, FFAs decreased in diabetic patients and control subjects (from 593 to 193 and from 460 to 162 micromol/l, respectively); GNG decreased (from 6.1 to 4.2 and from 4.7 to 3.5 micromol x kg(-1) x min(-1)), whereas GL decreased in diabetic patients (from 5.3 to 4.4 micromol x kg(-1) x min(-1)) but increased in control subjects (from 5.4 to 7.2 micromol x kg(-1) min(-1)). During the FFA rebound, FFAs increased in diabetic patients and control subjects (from 193 to 1,239 and from 162 to 1,491 micromol/l, respectively); GNG increased (from 4.2 to 5.4 and from 3.4 to 5.3 micromol x kg(-1) x min(-1) respectively), and GL decreased (from 4.4 to 3.4 and from 7.3 to 4.3 micromol x kg(-1) x min(-1), respectively). In summary, during an extended overnight fast, increasing plasma FFA levels stimulated GNG, whereas decreasing FFA levels inhibited GNG in both diabetic and control subjects; 20 h after the last meal, approximately one-third of GNG in both diabetic and control subjects was dependent on FFAs; and autoregulation of EGP by GL in response to decreasing GNG was impaired in diabetic patients.