Insulin inhibits glucose production by a direct effect in diabetic depancreatized dogs during euglycemia

2002 ◽  
Vol 283 (5) ◽  
pp. E1002-E1007 ◽  
Author(s):  
Neehar Gupta ◽  
Harmanjit Sandhu ◽  
Tracy Goh ◽  
Keyur Shah ◽  
Stephanie R. Wiesenthal ◽  
...  

In our previous studies in nondiabetic dogs and humans, insulin suppressed glucose production (GP) by both an indirect extrahepatic and a direct hepatic effect. However, insulin had no direct effect on GP in diabetic depancreatized dogs under conditions of moderate hyperglycemia. The present study was designed to investigate whether insulin can inhibit GP by a direct effect in this model under conditions of euglycemia. Depancreatized dogs were made euglycemic (∼6 mmol/l), rather than moderately hyperglycemic (∼10 mmol/l) as in our previous studies, by basal portal insulin infusion. After ∼100 min of euglycemia, a hyperinsulinemic euglycemic clamp was performed by giving an additional infusion of insulin either portally (POR) or peripherally at about one-half the rate (½ PER) to match the peripheral venous insulin concentrations. The greater hepatic insulin load in POR resulted in greater suppression of GP (from 16.5 ± 1.8 to 12.2 ± 1.6 μmol · kg−1 · min−1) than ½ PER (from 17.8 ± 1.9 to 15.6 ± 2.0 μmol · kg−1 · min−1, P < 0.001 vs. POR), consistent with insulin having a direct hepatic effect in suppressing GP. We conclude that the direct effect of insulin to inhibit GP is present in diabetic depancreatized dogs under conditions of acutely induced euglycemia. These results suggest that, in diabetes, the prevailing glycemic level is a determinant of the balance between insulin's direct and indirect effects on GP.

2020 ◽  
Vol 29 (13) ◽  
pp. 3669-3688
Author(s):  
Asunción Semper-Pascual ◽  
Julieta Decarre ◽  
Matthias Baumann ◽  
Micaela Camino ◽  
Yamil Di Blanco ◽  
...  

Abstract Land-use change is a global threat to biodiversity, but how land-use change affects species beyond the direct effect of habitat loss remains poorly understood. We developed an approach to isolate and map the direct and indirect effects of agricultural expansion on species of conservation concern, using the threatened giant anteater (Myrmecophaga tridactyla) in the Gran Chaco as an example. We reconstructed anteater occupancy change between 1985 and 2015 by fitting single-season occupancy models with contemporary camera-trap data and backcasting the models to 1985 and 2000 land-cover/use maps. Based on this, we compared the area of forest loss (direct effect of agricultural expansion) with the area where forests remained but occupancy still declined (indirect effect of agricultural expansion). Anteater occupancy decreased substantially since 1985, particularly after 2000 when agriculture expanded rapidly. Between 1985 and 2015, ~ 64,000 km2 of forest disappeared, yet occupancy declined across a larger area (~ 102,000 km2), extending far into seemingly untransformed habitat. This suggests that widespread sink habitat has emerged due to agricultural land-use change, and that species may lose their habitat through direct and indirect effects of agricultural expansion, highlighting the urgent need for broad-scale conservation planning in the Chaco. Appropriate management responses could proactively protect more habitat where populations are stable, and restore habitat or address causes of mortality in areas where declines occur. Our work also highlights how occupancy modelling combined with remote sensing can help to detect the direct and indirect effects of agricultural expansion, providing guidance for spatially targeting conservation strategies to halt extinctions.


2004 ◽  
Vol 32 (5) ◽  
pp. 449-458 ◽  
Author(s):  
Tülin Gençöz ◽  
Yeşim Özlale ◽  
Randy Lennon

The aim of this study was to investigate the direct and indirect effects of social support on psychological well-being. Social support was evaluated under two different categories which were named as Aid-Related and Appreciation-Related Socia+l Support. The first category was more related to potential for receiving help from others when needed, and being cared for by others, while the latter category was more related to being recognized by others as an efficient source of help and reassurance of worth. Undergraduate university students (N =342) served as subjects, and results revealed that aid-related social support and psychological well-being (i.e., alleviated depression symptoms) association was partially mediated by experiencing fewer life stresses. On the other hand, appreciation-related social support had a direct effect on psychological well-being. Implications of these results are discussed.


2014 ◽  
Vol 19 (2) ◽  
pp. 201-220 ◽  
Author(s):  
Scott Sigmund Gartner

Are Directive Strategies in international disputes the most effective mediation method for obtaining durable peace? A standard statistical analysis shows no effect of Directive Strategies on settlement durability. This result however, is misleading, failing to take selection and indirect effects into account. In this article, I identify when selection and process effects reinforce or oppose each other. Directive Strategies have opposing negative selection and positive process effects, which can distort inferences about their influence. Strategies’ direct and indirect effects are also examined. Directive Strategies are more likely to lead to Full Settlements – the most comprehensive form of agreement, which improve the settlement durability (an indirect effect). However, Directive Strategies are used in more intractable disputes that result in fragile settlements (a direct effect). A statistical analysis of international disputes that takes these conflicting dynamics into account demonstrates the efficacy of Directive Mediation Strategies in producing durable agreements.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Raluca Popa ◽  
Radu Sascau ◽  
Cristian Statescu ◽  
Vlad Vasiliu ◽  
Andreea Neamtu ◽  
...  

Abstract Background and Aims Despite impressive improvements in treatment strategies, heart failure (HF) morbidity and mortality remain substantially high worldwide. Pulmonary congestion is considered the leading cause for hospital admissions and death among patients with HF. The aim of this study is to investigate if the effect of fluid status, as assessed by bioimpedance spectroscopy (BIS) on lung congestion is mediated by renal function, inflammation or cardiac function. Method This was a prospective observational study of outpatient adults referred for clinically indicated transthoracic echocardiograms at an academic hospital between 2016 and 2018. A left ventricular ejection fraction (LVEF) below 45% was required for inclusion (HFrEF). Mediation is the process through which an exposure causes disease. We hypothesized that some of the total effect of extracellular water (ECW) to intracellular water (ICW) (as assessed by bioimpedance) ratio on lung congestion (as assessed by lung ultrasonography) is mediated by C-reactive protein (CRP), left atrium volum index (LAVI) or estimated glomerular filtration rate (eGFR) – the mediators. Results Our study included 153 patients. The mean age and eGFR values of the population at baseline were 67.1 years and 66.5 ml/min/1.73m2. The mean median value for CRP was 25.6 (IQR 9.0-56.4) mg/L. Figure 1 depicts the structural equation models with the calculated magnitude of the direct and indirect effects of ECW/ICW on the B-lines number in our population. In this model, the fluid status has both direct and indirect effects on lung congestion. Specifically, it has a direct effect on LAVI and eGFR, which in turn have a direct effect on the number of B-lines. Therefore, the indirect effect mediated by LAVI and eGFR accounts for a significant proportion of 27.6% of the total effect of ECW/ICW on lung congestion Although ECW/ICW has a direct effect on inflammation, this doesn’t have any effect on renal function or lung congestion. Conclusion We show that eGFR and LAVI partly mediate the effect of ECW/ICW on lung congestion in patients with HFrEF. While the deleterious effects of fluid overload on lung congestion have long been recognized, this study provides evidence for a relationship of significant magnitude linking fluid overload with decreased eGFR and increased LAVI, which in turn lead to elevations in the B-lines number. This work was supported by a grant of the Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P1-1.1-PD-2016-0287, within PNCDI III and by a grant of the “Grigore T. Popa” University of Medicine and Pharmacy, contract number 27505/2018.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hui Wu ◽  
Chunhua Sui ◽  
Hui Xu ◽  
Fangzhen Xia ◽  
Hualing Zhai ◽  
...  

Objective. Glucagon-like peptide-1 (GLP-1) analogues (e.g., exenatide) increase insulin secretion in diabetes but less is known about their effects on glucose production or insulin-stimulated glucose uptake in peripheral tissues.Methods. Four groups of Sprague-Dawley rats were studied: nondiabetic (control, C); nondiabetic + exenatide (C + E); diabetic (D); diabetic + exenatide (D + E) with diabetes induced by streptozotocin and high fat diet. Infusion of 3-3H-glucose and U-13C-glycerol was used to measure basal rates of appearance (Ra) of glucose and glycerol and gluconeogenesis from glycerol (GNG). During hyperinsulinemic-euglycemic clamp, glucose uptake into gastrocnemius muscles was measured with 2-deoxy-D-14C-glucose.Results. In the diabetic rats, exenatide reduced the basalRaof glucose (P<0.01) and glycerol (P<0.01) and GNG (P<0.001). During the clamp,Raof glucose was also reduced, whereas the rate of disappearance of glucose increased and there was increased glucose uptake into muscle (P<0.01) during the clamp. In the nondiabetic rats, exenatide had no effect.Conclusion. In addition to its known effects on insulin secretion, administration of the GLP-1 analogue, exenatide, is associated with increased inhibition of gluconeogenesis and improved glucose uptake into muscle in diabetic rats, implying improved hepatic and peripheral insulin sensitivity.


1970 ◽  
Vol 9 (1-2) ◽  
pp. 89-98 ◽  
Author(s):  
KK Paul ◽  
MA Bari

Thirty accessions of taro (Colocasia esculenta L) varieties were evaluated to estimate the direct and indirect effects of different plant characters, namely, plant height, petiole length, petiole breadth, leaf number, leaf length, leaf breadth, LAI, inflorescence length, peduncle length, corm length, corm breadth, cormel number, cormel length, cormel breadth, corm weight, cormel weight on yield per plant. Plant height, petiole length, corm breadth, cormel number, cormel length exhibited direct effect on yield per plant at the genotypic level. Cormel weight and cormel breadth had the highest direct effect on yield per plant at the phenotypic level. The residual effect was 0.3043 at the genotypic level and that at phenotypic level was 0.4874. Keywords: Colocasia esculenta; direct effect; indirect effect; yield of taro DOI: http://dx.doi.org/10.3329/agric.v9i1-2.9483 The Agriculturists 2011; 9(1&2): 89-98


2015 ◽  
Vol 6 (1) ◽  
Author(s):  
InSug O-Sullivan ◽  
Wenwei Zhang ◽  
David H. Wasserman ◽  
Chong Wee Liew ◽  
Jonathan Liu ◽  
...  

Metabolomics ◽  
2021 ◽  
Vol 17 (6) ◽  
Author(s):  
Wenyi Wang ◽  
Ko Willems van Dijk ◽  
Carolien A. Wijsman ◽  
Maarten P. Rozing ◽  
Simon P. Mooijaart ◽  
...  

Abstract Background Insulin is the key regulator of glucose metabolism, but it is difficult to dissect direct insulin from glucose-induced effects. We aimed to investigate the effects of hyperinsulemia on metabolomic measures under euglycemic conditions in nondiabetic participants. Methods We assessed concentrations of 151 metabolomic measures throughout a two-step hyperinsulinemic euglycemic clamp procedure. We included 24 participants (50% women, mean age = 62 [s.d. = 4.2] years) and metabolomic measures were assessed under baseline, low-dose (10 mU/m2/min) and high-dose (40 mU/m2/min) insulin conditions. The effects of low- and high-dose insulin infusion on metabolomic measures were analyzed using linear mixed-effect models for repeated measures. Results After low-dose insulin infusion, 90 metabolomic measures changed in concentration (p < 1.34e−4), among which glycerol (beta [Confidence Interval] =  − 1.41 [− 1.54, − 1.27] s.d., p = 1.28e−95) and three-hydroxybutyrate (− 1.22 [− 1.36, − 1.07] s.d., p = 1.44e−61) showed largest effect sizes. After high-dose insulin infusion, 121 metabolomic measures changed in concentration, among which branched-chain amino acids showed the largest additional decrease compared with low-dose insulin infusion (e.g., Leucine, − 1.78 [− 1.88, − 1.69] s.d., P = 2.7e−295). More specifically, after low- and high-dose insulin infusion, the distribution of the lipoproteins shifted towards more LDL-sized particles with decreased mean diameters. Conclusion Metabolomic measures are differentially insulin sensitive and may thus be differentially affected by the development of insulin resistance. Moreover, our data suggests insulin directly affects metabolomic measures previously associated with increased cardiovascular disease risk.


2016 ◽  
Vol 26 (47) ◽  
pp. 672
Author(s):  
Adriana De Miranda-Ribeiro ◽  
Ricardo Alexandrino Garcia ◽  
Carlos Lobo

<p>No cenário das migrações no Brasil, o retorno ao local de nascimento tem crescido de importância nas últimas décadas. Este artigo tem como objetivo principal a mensuração dos efeitos direto e indireto da migração de retorno às unidades da Federação brasileira, no período 2000-2010. Foram utilizados os microdados do Censo Demográfico de 2010. A metodologia denomina de efeito direto os retornados ao local de nascimento. O efeito indireto é composto por parentes do retornado, desde que cumpram alguns requisitos. Os resultados apontam que a soma dos efeitos diretos e indiretos da migração de retorno correspondem a quase a metade dos imigrantes de última etapa do país.</p><p><strong>Abstract </strong></p><p>The return to the place of birth plays an important role in the Brazilian migration scenario. This paper measures the direct and indirect effects of return migration in Brazil between 2000 and 2010. Data come from the 2010 Brazilian Demographic Census. Those who return to the place of birth compose the direct effect. The indirect effect is composed by the returned migrant’s relatives, conditioned to some rules.  Results show that the return migration effects in Brazil represent almost a half of the Brazilian immigrants in the period.</p><p><strong>Keywords</strong>: spatial distribution, internal migration, return migration.</p>


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