Evaluation of the specific effects of intranasal glucagon on glucose production and lipid concentration in healthy men during a pancreatic clamp

2017 ◽  
Vol 20 (2) ◽  
pp. 328-334 ◽  
Author(s):  
Satya Dash ◽  
Changting Xiao ◽  
Priska Stahel ◽  
Khajag Koulajian ◽  
Adria Giacca ◽  
...  
2019 ◽  
Vol 40 (5) ◽  
pp. 1394-1423 ◽  
Author(s):  
Jonathan D Douros ◽  
Jenny Tong ◽  
David A D’Alessio

AbstractAlthough bariatric surgery was developed primarily to treat morbid obesity, evidence from the earliest clinical observations to the most recent clinical trials consistently demonstrates that these procedures have substantial effects on glucose metabolism. A large base of research indicates that bariatric surgeries such as Roux-en-Y gastric bypass (RYGB), vertical sleeve gastrectomy (VSG), and biliopancreatic diversion (BPD) improve diabetes in most patients, with effects frequently evident prior to substantial weight reduction. There is now unequivocal evidence from randomized controlled trials that the efficacy of surgery is superior to intensive life-style/medical management. Despite advances in the clinical understanding and application of bariatric surgery, there remains only limited knowledge of the mechanisms by which these procedures confer such large changes to metabolic physiology. The improvement of insulin sensitivity that occurs with weight loss (e.g., the result of diet, illness, physical training) also accompanies bariatric surgery. However, there is evidence to support specific effects of surgery on insulin clearance, hepatic glucose production, and islet function. Understanding the mechanisms by which surgery affects these parameters of glucose regulation has the potential to identify new targets for therapeutic discovery. Studies to distinguish among bariatric surgeries on key parameters of glucose metabolism are limited but would be of considerable value to assist clinicians in selecting specific procedures and investigators in delineating the resulting physiology. This review is based on literature related to factors governing glucose metabolism and insulin secretion after the commonly used RYGB and VSG, and the less frequently used BPD and adjustable gastric banding.


1997 ◽  
Vol 273 (2) ◽  
pp. E315-E320 ◽  
Author(s):  
P. Tounian ◽  
P. Schneiter ◽  
S. Henry ◽  
J. Delarue ◽  
L. Tappy

This study was designed to determine whether glucocorticoids alter autoregulation of glucose production and fructose metabolism. Two protocols with either dexamethasone (DEX) or placebo (Placebo) were performed in six healthy men during hourly ingestion of[13C]fructose (1.33 mmol.kg-1.h-1) for 3 h. In both protocols, endogenous glucose production (EGP) increased by 8 (Placebo) and 7% (DEX) after fructose, whereas gluconeogenesis from fructose represented 82 (Placebo) and 72% (DEX) of EGP. Fructose oxidation measured from breath 13CO2 was similar in both protocols [9.3 +/- 0.7 (Placebo) and 9.6 +/- 0.5 mumol.kg-1.min-1 (DEX)]. Nonoxidative carbohydrate disposal, calculated as fructose administration rate minus net carbohydrate oxidation rate after fructose ingestion measured by indirect calorimetry, was also similar in both protocols [5.8 +/- 0.8 (Placebo) and 5.9 +/- 2.0 mumol.kg-1.min-1 (DEX)]. We concluded that dexamethasone 1) does not alter the autoregulatory process that prevents a fructose-induced increase in gluconeogenesis from increasing total glucose production and 2) does not affect oxidative and nonoxidative pathways of fructose. This indicates that the insulin-regulated enzymes involved in these pathways are not affected in a major way by dexamethasone.


Author(s):  
Sergio A. Burgos ◽  
Stéphanie Chevalier ◽  
José A. Morais ◽  
Marie Lamarche ◽  
Samantha Kellett ◽  
...  

Elevated circulating amino acid (AA) concentrations are purported to cause insulin resistance (IR) in humans. To quantify hyperaminoacidemia effects on insulin-mediated glucose turnover in healthy men, we performed two-stage pancreatic clamps using octreotide with glucagon and growth hormone replacement. In the basal stage, insulin was infused to maintain euglycemia at postabsorptive levels. During the clamp stage, insulin was raised to postprandial levels, glycemia clamped at 5.5 mmol/L by glucose infusion and branched-chain AA (BCAA) maintained at either postabsorptive (Hyper1; n=8) or postprandial (Hyper2; n=7) by AA infusion. Glucose turnover was measured by D-3-[3H]glucose dilution. Octreotide suppressed C-peptide; glucagon, growth hormone and glycemia were maintained at postabsorptive levels throughout. Insulin did not differ at postabsorptive (72±5 vs. 60±5 pmol/L; Hyper1 vs. Hyper2) and increased to similar concentrations at basal (108±11 vs. 106±14) and clamp stages (551±23 vs. 540±25). Postabsorptive BCAA were maintained during Hyper1 and increased >2-fold (830±26 µmol/L) during Hyper2. Endogenous glucose production was similarly suppressed (0.95±0.16 vs. 1.37±0.23 mg/kg lean body mass/min; Hyper1 vs. Hyper2) and basal glucose disposal (3.44±0.12 vs. 3.67±0.14) increased to similar levels (10.89±0.56 vs. 11.11±1.00) during the clamp. Thus, acute physiological elevation of AA did not cause IR in healthy men. NOVELTY • A two-step pancreatic clamp was used to quantify the effect of amino acids on insulin sensitivity in humans. • Acute physiological elevation of circulating amino acids does not cause insulin resistance in healthy men.


2010 ◽  
Vol 299 (2) ◽  
pp. H248-H256 ◽  
Author(s):  
Nastassia M. Navasiolava ◽  
Françoise Dignat-George ◽  
Florence Sabatier ◽  
Irina M. Larina ◽  
Claire Demiot ◽  
...  

A sedentary lifestyle has adverse effects on the cardiovascular system, including impaired endothelial functions. Subjecting healthy men to 7 days of dry immersion (DI) presented a unique opportunity to analyze the specific effects of enhanced inactivity on the endothelium. We investigated endothelial properties before, during, and after 7 days of DI involving eight subjects. Microcirculatory functions were assessed with laser Doppler in the skin of the calf. We studied basal blood flow and endothelium-dependent and -independent vasodilation. We also measured plasma levels of microparticles, a sign of cellular dysfunction, and soluble endothelial factors, reflecting the endothelial state. Basal flow and endothelium-dependent vasodilation were reduced by DI (22 ± 4 vs. 15 ± 2 arbitrary units and 29 ± 6% vs. 12 ± 6%, respectively, P < 0.05), and this was accompanied by an increase in circulating endothelial microparticles (EMPs), which was significant on day 3 (42 ± 8 vs. 65 ± 10 EMPs/μl, P < 0.05), whereas microparticles from other cell origins remained unchanged. Plasma soluble VEGF decreased significantly during DI, whereas VEGF receptor 1 and soluble CD62E were unchanged, indicating that the increase in EMPs was associated with a change in antiapoptotic tone rather than endothelial activation. Our study showed that extreme physical inactivity in humans induced by 7 days of DI causes microvascular impairment with a disturbance of endothelial functions, associated with a selective increase in EMPs. Microcirculatory endothelial dysfunction might contribute to cardiovascular deconditioning as well as to hypodynamia-associated pathologies. In conclusion, the endothelium should be the focus of special care in situations of acute limitation of physical activity.


2019 ◽  
Vol 476 (24) ◽  
pp. 3687-3704 ◽  
Author(s):  
Aphrodite T. Choumessi ◽  
Manuel Johanns ◽  
Claire Beaufay ◽  
Marie-France Herent ◽  
Vincent Stroobant ◽  
...  

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze–thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKβ1−/− mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.


2010 ◽  
Vol 34 (8) ◽  
pp. S12-S12
Author(s):  
Hong‑Ge Li ◽  
Chen Min Xu ◽  
Kun Li ◽  
Ya Ni ◽  
Wen‑Ying Chen ◽  
...  

2016 ◽  
Vol 75 (3) ◽  
pp. 133-140
Author(s):  
Robert Busching ◽  
Johannes Lutz

Abstract. Legally irrelevant information like facial features is used to form judgments about rape cases. Using a reverse-correlation technique, it is possible to visualize criminal stereotypes and test whether these representations influence judgments. In the first step, images of the stereotypical faces of a rapist, a thief, and a lifesaver were generated. These images showed a clear distinction between the lifesaver and the two criminal representations, but the criminal representations were rather similar. In the next step, the images were presented together with rape scenarios, and participants (N = 153) indicated the defendant’s level of liability. Participants with high rape myth acceptance scores attributed a lower level of liability to a defendant who resembled a stereotypical lifesaver. However, no specific effects of the image of the stereotypical rapist compared to the stereotypical thief were found. We discuss the findings with respect to the influence of visual stereotypes on legal judgments and the nature of these mental representations.


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