scholarly journals Reward signalling in brainstem nuclei under glycemic flux

2018 ◽  
Author(s):  
Tobias Morville ◽  
Kristoffer Madsen ◽  
Hartwig R. Siebner ◽  
Oliver J. Hulme
Keyword(s):  
Serum Glucose ◽  
Neural Encoding ◽  
Conditioning Paradigm ◽  
Glucose Levels ◽  
Naturally Occurring ◽  
Physiological Serum ◽  
Human Volunteers ◽  
Parabrachial Nuclei ◽  
Primary Reward ◽  
Homeostatic State

Phasic dopamine release from mid-brain dopaminergic neurons signals errors of reward prediction (RPE). If reward maximisation is to maintain homeostasis, then the value of primary rewards should be coupled to the homeostatic errors they remediate. This leads to the prediction that RPE signals should be configured as a function of homeostatic state and thus, diminish with the attenuation of homeostatic error. To test this hypothesis, we collected a large volume of functional MRI data from five human volunteers on four separate days. After fasting for 12 hours, subjects consumed preloads that differed in glucose concentration. Participants then underwent a Pavlovian cue-conditioning paradigm in which the colour of a fixation-cross was stochastically associated with the delivery of water or glucose via a gustometer. This design afforded computation of RPE separately for better- and worse-than expected outcomes during ascending and descending trajectories of physiological serum glucose fluctuations. In the parabrachial nuclei, variations in regional activity coding positive RPEs scaled positively with serum glucose for ascending and descending glucose levels. The ventral tegmental area and substantia nigra became more sensitive to negative RPEs when glucose levels were ascending. Together, the results show that RPE signals in key brainstem structures are modulated by homeostatic trajectories of naturally occurring glycemic flux, revealing a tight interplay between homeostatic state and the neural encoding of primary reward in the human brain.

scholarly journals Reward signalling in brainstem nuclei under fluctuating blood glucose

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0243899
Author(s):  
Tobias Morville ◽  
Kristoffer H. Madsen ◽  
Hartwig R. Siebner ◽  
Oliver J. Hulme
Keyword(s):  
Dopaminergic Neurons ◽  
Serum Glucose ◽  
Neural Encoding ◽  
Conditioning Paradigm ◽  
Glucose Levels ◽  
Naturally Occurring ◽  
Human Volunteers ◽  
Parabrachial Nuclei ◽  
Primary Reward ◽  
Homeostatic State

Phasic dopamine release from mid-brain dopaminergic neurons is thought to signal errors of reward prediction (RPE). If reward maximisation is to maintain homeostasis, then the value of primary rewards should be coupled to the homeostatic errors they remediate. This leads to the prediction that RPE signals should be configured as a function of homeostatic state and thus diminish with the attenuation of homeostatic error. To test this hypothesis, we collected a large volume of functional MRI data from five human volunteers on four separate days. After fasting for 12 hours, subjects consumed preloads that differed in glucose concentration. Participants then underwent a Pavlovian cue-conditioning paradigm in which the colour of a fixation-cross was stochastically associated with the delivery of water or glucose via a gustometer. This design afforded computation of RPE separately for better- and worse-than expected outcomes during ascending and descending trajectories of serum glucose fluctuations. In the parabrachial nuclei, regional activity coding positive RPEs scaled positively with serum glucose for both ascending and descending glucose levels. The ventral tegmental area and substantia nigra became more sensitive to negative RPEs when glucose levels were ascending. Together, the results suggest that RPE signals in key brainstem structures are modulated by homeostatic trajectories of naturally occurring glycaemic flux, revealing a tight interplay between homeostatic state and the neural encoding of primary reward in the human brain.

scholarly journals Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats

2014 ◽  
Vol 79 (1) ◽  
pp. 109-116 ◽  
Author(s):  
Fuminori Kawabata ◽  
Takafumi Mizushige ◽  
Keisuke Uozumi ◽  
Kohsuke Hayamizu ◽  
Li Han ◽  
...  
Keyword(s):  
Protein Intake ◽  
Muscle Hypertrophy ◽  
Serum Glucose ◽  
Fast Muscle ◽  
Fish Protein ◽  
Liver Lipids ◽  
Glucose Levels

Treatment of feline diabetes mellitus using an α-glucosidase inhibitor and a low-carbohydrate diet

2003 ◽  
Vol 5 (3) ◽  
pp. 183-189 ◽  
Author(s):  
EM Mazzaferro ◽  
DS Greco ◽  
AS Turner ◽  
MJ Fettman
Keyword(s):  
Diabetes Mellitus ◽  
Body Fat ◽  
Effective Means ◽  
Serum Glucose ◽  
Carbohydrate Diet ◽  
Low Carbohydrate Diet ◽  
Glucosidase Inhibitor ◽  
Naturally Occurring ◽  
Insulin Dependence ◽  
Low Carbohydrate

The purpose of this study was to determine the effect of an α-glucosidase inhibitor (acarbose), combined with a low-carbohydrate diet on the treatment of naturally occurring diabetes mellitus in cats. Eighteen client-owned cats with naturally occurring diabetes mellitus were entered into the study. Dual-energy X-ray absorptiometry (DEXA) was performed prior to and 4 months after feeding the diet to determine total body composition, including lean body mass (LBM) and percent body fat. Each cat was fed a commercially available low-carbohydrate canned feline diet and received 12.5 mg/cat acarbose orally every 12 h with meals. All cats received subcutaneous insulin therapy except one cat in the study group that received glipizide (5 mg BID PO). Monthly serum glucose and fructosamine concentrations were obtained, and were used to adjust insulin doses based on individual cat's requirements. Patients were later classified as responders (insulin was discontinued, n=11) and non-responders (continued to require insulin or glipizide, n=7). Responders were initially obese (<28% body fat) and non-responders had significantly less body fat than responders (<28% body fat). Serum fructosamine and glucose concentrations decreased significantly in both responder and non-responder groups over the course of 4 months of therapy. Better results were observed in responder cats, for which exogenousinsulin therapy was discontinued, glycemic parameters improved, and body fat decreased. In non-responders, median insulin requirements decreased and glycemic parameters improved significantly, despite continued insulin dependence. The use a low-carbohydrate diet with acarbose was an effective means of decreasing exogenous insulin dependence and improving glycemiccontrol in a series of client-owned cats with naturally occurring diabetes mellitus.

Time-dependent effect of an oral hypoglycemic agent upon serum glucose levels

1973 ◽  
Vol 10 (4) ◽  
pp. 841-851
Author(s):  
Juan J. Gagliardino ◽  
María T. Pessacq ◽  
Oscar Marcote ◽  
Elma E. Gagliardino
Keyword(s):  
Serum Glucose ◽  
Time Dependent ◽  
Oral Hypoglycemic Agent ◽  
Dependent Effect ◽  
Glucose Levels ◽  
Hypoglycemic Agent ◽  
Time Dependent Effect

scholarly journals Characterization of hyperglycemia due to sub-chronic administration of red ginseng extract via comparative global proteomic analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ann-Yae Na ◽  
Jung Jae Jo ◽  
Oh Kwang Kwon ◽  
Piljoung Cho ◽  
Yan Gao ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
Herbal Remedy ◽  
Chronic Administration ◽  
Serum Glucose ◽  
Control Group ◽  
Red Ginseng ◽  
Korean Red Ginseng ◽  
Ginseng Extract ◽  
Glucose Levels ◽  
Term Administration

AbstractGinseng (Panax ginseng Meyer) is commonly used as an herbal remedy worldwide. Few studies have explored the possible physiological changes in the liver although patients often self-medicate with ginseng preparations, which may lead to exceeding the recommended dose for long-term administration. Here, we analyzed changes in the hepatic proteins of mouse livers using quantitative proteomics after sub-chronic administration of Korean red ginseng (KRG) extract (control group and 0.5, 1.0, and 2.0 g/kg KRG) using tandem mass tag (TMT) 6‐plex technology. The 1.0 and 2.0 g/kg KRG groups exhibited signs of liver injury, including increased levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) in the serum. Furthermore, serum glucose levels were significantly higher following KRG administration compared with the control group. Based on the upregulated proteins found in the proteomic analysis, we found that increased cystathionine beta-synthase (CBS) and cystathionine gamma-lyase (CSE) levels promoted greater hydrogen sulfide (H2S) synthesis in the liver. This investigation provides novel evidence that sub-chronic administration of KRG can elevate H2S production by increasing protein expression of CBS and CSE in the liver.

scholarly journals The Frequent Adiponutrin (PNPLA3) Variant p.Ile148Met Is Associated with Early Liver Injury: Analysis of a German Pediatric Cohort

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Marcin Krawczyk ◽  
Roman Liebe ◽  
Ina B. Maier ◽  
Anna Janina Engstler ◽  
Frank Lammert ◽  
...  
Keyword(s):  
Liver Injury ◽  
Serum Glucose ◽  
Normal Weight ◽  
Study Cohort ◽  
Overweight Children ◽  
Entire Study ◽  
Metabolic Traits ◽  
Glucose Levels ◽  
The Common ◽  
German Children

Introduction.The common adiponutrin (PNPLA3) variant p.Ile148Met is associated with liver injury. Here, we investigate the association of this polymorphism with hepatic and metabolic traits in a pediatric cohort.Patients and Methods.The study cohort comprised 142 German children (age 5–9 years, 98 overweight, 19 children with NAFLD).Results.Overweight children presented with increased serum ALT (P=0.001) and GGT (P<0.001) activities. ALT activities differed significantly (P=0.02) between carriers of differentPNPLA3genotypes in the entire study cohort, in normal weight children (P=0.02) and in children younger than 7 years (P=0.02). Carriers of the prosteatoticPNPLA3genotype p.148Met/Met displayed higher ALT activities as compared to children with the frequent genotype p.148Ile/Ile (P=0.01). The BMI was however a stronger predictor of ALT activities compared to thePNPLA3genotype (P<0.001andP=0.06, resp.). The variant was associated with increased serum glucose levels (P=0.01) and HOMA index (P=0.02) in carriers of the p.148Ile/Met genotype but did not affect other metabolic traits or the presence of NAFLD.Discussion.The frequentPNPLA3variant p.Ile148Met is associated with serum ALT activities already at a young age.

Hypothalamic noradrenergic and sympathoadrenal control of glycemia after stress

1989 ◽  
Vol 256 (2) ◽  
pp. E231-E235
Author(s):  
G. A. Smythe ◽  
W. S. Pascoe ◽  
L. H. Storlien
Keyword(s):  
Insulin Release ◽  
Acute Stress ◽  
Serum Insulin ◽  
Elevated Serum ◽  
Serum Glucose ◽  
Neural Pathways ◽  
Swim Stress ◽  
Insulin Levels ◽  
Glucose Levels ◽  
Positive Correlations

Central noradrenergic pathways play a significant role in mediating blood glucose levels after neuroglycopenia. To further investigate hypothalamic noradrenergic neuronal activity (NNA) and sympathoadrenal influences in glucoregulation, we studied the effects of acute stress on glycemia and insulin release in normal and adrenalectomized (ADRX) rats. Within 5 min of exposure of rats to ether or cold-swim stress, significant positive correlations were evident between hypothalamic NNA and serum glucose levels (r = 0.70, P less than 0.001; at 15 min r = 0.78, P less than 0.0001). Five minutes after stress in the intact rat, insulin release was inhibited and serum insulin levels inversely correlated to hypothalamic NNA (r = 0.45, P less than 0.05). This relationship between insulin and NNA was no longer present 15 min after stress, but the levels of insulin remained inappropriately low with respect to the elevated serum glucose levels (approximately 30% above basal). Blockade of sympathetic noradrenergic pathways by treatment of intact rats with guanethidine prevented the rise in glucose after cold-swim stress but did not prevent the inhibition of insulin release. Fifteen minutes after exposure of ADRX rats to cold-swim stress their hypothalamic NNA and serum glucose levels were similar to intact animals. However, in contrast to their intact counterparts, serum insulin levels were significantly elevated (P less than 0.01). These data are consistent with central noradrenergic neural pathways directly mediating hepatic glucose release and indirectly inhibiting pancreatic insulin release via activation of adrenal medullary catecholamines.

scholarly journals Endothelial dysfunction precedes hypertension in diet-induced insulin resistance

1998 ◽  
Vol 275 (3) ◽  
pp. R788-R792 ◽  
Author(s):  
Prasad V. G. Katakam ◽  
Michael R. Ujhelyi ◽  
Margarethe E. Hoenig ◽  
Allison Winecoff Miller
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Serum Insulin ◽  
Serum Glucose ◽  
Mesenteric Arteries ◽  
Control Group ◽  
Sprague Dawley ◽  
Insulin Resistant ◽  
Glucose Levels

The insulin-resistant (IR) syndrome may be an impetus for the development of hypertension (HTN). Unfortunately, the mechanism by which this could occur is unclear. Our laboratory and others have described impaired endothelium-mediated relaxation in IR, mildly hypertensive rats. The purpose of the current study is to determine if HTN is most likely a cause or result of impaired endothelial function. Sprague-Dawley rats were randomized to receive a fructose-rich diet for 3, 7, 10, 14, 18, or 28 days or were placed in a control group. The control group received rat chow. After diet treatment, animals were instrumented with arterial cannulas, and while awake and unrestrained, their blood pressure (BP) was measured. Subsequently, endothelium-mediated relaxation to acetylcholine was determined (in vitro) by measuring intraluminal diameter of phenylephrine-preconstricted mesenteric arteries (∼250 μM). Serum insulin levels were significantly elevated in all groups receiving fructose feeding compared with control, whereas there were no differences in serum glucose levels between groups. Impairment of endothelium-mediated relaxation starts by day 14 [mean percent maximal relaxation (Emax): 69 ± 10% of baseline] and becomes significant by day 18 (Emax: 52 ± 11% of baseline; P < 0.01). However, the mean BP (mmHg) does not become significantly elevated until day 28 [BP: 132 ± 1 ( day 28) vs. 116 ± 3 (control); P < 0.05]. These findings demonstrate that both IR and endothelial dysfunction occur before HTN in this model and suggest that endothelial dysfunction may be a mechanism linking insulin resistance and essential HTN.

scholarly journals Dexamethasone Administration in Mice Leads to Less Body Weight Gain over Time, Lower Serum Glucose, and Higher Insulin Levels Independently of NRF2

Antioxidants ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 4
Author(s):  
Fotini Filippopoulou ◽  
George I. Habeos ◽  
Vagelis Rinotas ◽  
Antonia Sophocleous ◽  
Gerasimos P. Sykiotis ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Molecular Mechanisms ◽  
Inflammatory Diseases ◽  
Body Weight Gain ◽  
Serum Glucose ◽  
Dexamethasone Treatment ◽  
Insulin Levels ◽  
Glucose Levels ◽  
High Insulin

Glucocorticoids are used widely on a long-term basis in autoimmune and inflammatory diseases. Their adverse effects include the development of hyperglycemia and osteoporosis, whose molecular mechanisms have been only partially studied in preclinical models. Both these glucocorticoid-induced pathologies have been shown to be mediated at least in part by oxidative stress. The transcription factor nuclear erythroid factor 2-like 2 (NRF2) is a central regulator of antioxidant and cytoprotective responses. Thus, we hypothesized that NRF2 may play a role in glucocorticoid-induced metabolic disease and osteoporosis. To this end, WT and Nrf2 knockout (Nrf2KO) mice of both genders were treated with 2 mg/kg dexamethasone or vehicle 3 times per week for 13 weeks. Dexamethasone treatment led to less weight gain during the treatment period without affecting food consumption, as well as to lower glucose levels and high insulin levels compared to vehicle-treated mice. Dexamethasone also reduced cortical bone volume and density. All these effects of dexamethasone were similar between male and female mice, as well as between WT and Nrf2KO mice. Hepatic NRF2 signaling and gluconeogenic gene expression were not affected by dexamethasone. A 2-day dexamethasone treatment was also sufficient to increase insulin levels without affecting body weight and glucose levels. Hence, dexamethasone induces hyperinsulinemia, which potentially leads to decreased glucose levels, as well as osteoporosis, both independently of NRF2.

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