scholarly journals Brain Glucose Overexposure and Lack of Acute Metabolic Flexibility in Obesity and Type 2 Diabetes: A PET-[18F]FDG Study in Zucker and ZDF Rats

2010 ◽  
Vol 30 (5) ◽  
pp. 895-899 ◽  
Author(s):  
Tiziana Liistro ◽  
Letizia Guiducci ◽  
Silvia Burchielli ◽  
Daniele Panetta ◽  
Nicola Belcari ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Study Data ◽  
Mass Action ◽  
Glucose Disposal ◽  
Brain Glucose ◽  
Positron Emission ◽  
Obesity And Diabetes ◽  
Glucose Intake ◽  
High Fasting Glucose ◽  
And Control

Brain glucose exposure may complicate diabetes and obesity. We used positron emission tomography with 18F-fluorodeoxyglucose in Zucker obese, diabetic, and control rats to determine the contributions of blood glucose mass action versus local mechanisms in regulating central glucose disposal in fasted and acutely glucose-stimulated states, and their adaptations in obesity and diabetes. Our study data indicate that brain glucose uptake is dependent on both local and mass action components, and is stimulated by acute glucose intake in healthy rats. In diseased animals, the organ was chronically overexposed to glucose, due to high fasting glucose uptake, almost abolishing the physiologic response to glucose loading.

scholarly journals The Obesity Risk SNP (rs17782313) near the MC4R Gene Is Not Associated with Brain Glucose Uptake during Insulin Clamp—A Study in Finns

2021 ◽  
Vol 10 (6) ◽  
pp. 1312
Author(s):  
Eleni Rebelos ◽  
Miikka-Juhani Honka ◽  
Laura Ekblad ◽  
Marco Bucci ◽  
Jarna C. Hannukainen ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Statistical Parametric Mapping ◽  
Obesity Risk ◽  
Melanocortin System ◽  
Single Nucleotide ◽  
Brain Glucose ◽  
Mc4r Gene ◽  
Insulin Clamp ◽  
Positron Emission ◽  
Fractional Uptake

The melanocortin system is involved in the control of adiposity through modulation of food intake and energy expenditure. The single nucleotide polymorphism (SNP) rs17782313 near the MC4R gene has been linked to obesity, and a previous study using magnetoencephalography has shown that carriers of the mutant allele have decreased cerebrocortical response to insulin. Thus, in this study, we addressed whether rs17782313 associates with brain glucose uptake (BGU). Here, [18F]-fluorodeoxyglucose positron emission tomography (PET) data from 113 Finnish subjects scanned under insulin clamp conditions who also had the rs17782313 determined were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. Statistical analysis was performed with statistical parametric mapping. There was no difference in age, BMI, and insulin sensitivity as indexed by the M value between the rs17782313-C allele carriers and non-carriers. Brain glucose uptake during insulin clamp was not different by gene allele, and it correlated with the M value, in both the rs17782313-C allele carriers and non-carriers. The obesity risk SNP rs17782313 near the MC4R gene is not associated with brain glucose uptake during insulin clamp in humans, and this frequent mutation cannot explain the enhanced brain glucose metabolic rates in insulin resistance.

Effect of glycemia and nonesterified fatty acids on forearm glucose uptake in normal humans

1991 ◽  
Vol 261 (3) ◽  
pp. E304-E311 ◽  
Author(s):  
M. Walker ◽  
G. R. Fulcher ◽  
C. F. Sum ◽  
H. Orskov ◽  
K. G. Alberti
Keyword(s):  
Fatty Acid ◽  
Blood Glucose ◽  
Glucose Uptake ◽  
Whole Body ◽  
Glucose Disposal ◽  
Nonesterified Fatty Acid ◽  
Nonesterified Fatty Acids ◽  
Glucose Levels ◽  
And Control ◽  
Blood Glucose Concentrations

The purpose of this study was to examine the effect of physiological plasma nonesterified fatty acid (NEFA) levels on insulin-stimulated forearm and whole body glucose uptake and substrate oxidation during euglycemia and hyperglycemia. Seven healthy men received Intralipid and heparin for 210 min in two studies, with saline as control in two further studies. Insulin (0.05 U.kg-1.h-1) was infused from 60 min, and euglycemia was maintained during lipid (EL) and control (EC) studies, and hyperglycemia was maintained in the other studies (HL and HC). Forearm NEFA uptake was comparable in the lipid studies (+61 +/- 10 and +52 +/- 8 nmol.100 ml forearm-1.min-1, EL and HL) and was suppressed in the controls. With Intralipid, forearm glucose uptake decreased during euglycemia but not during hyperglycemia (+3.85 +/- 0.34 vs. +3.34 +/- 0.25 mumol.100 ml forearm-1.min-1, EC vs. EL, P less than 0.02), with comparable changes in whole body glucose uptake. Glucose oxidation and forearm alanine release decreased with Intralipid at both blood glucose levels, with no significant change in the rates of nonoxidative glucose disposal. These observations support the operation of the glucose-fatty acid cycle at physiological plasma NEFA levels at both blood glucose concentrations, but this was associated with a decrease in peripheral insulin sensitivity only during euglycemia.

scholarly journals Central GLP-1 contributes to improved cognitive function and brain glucose uptake after duodenum-jejunum bypass on obese and diabetic rats

2021 ◽  
Author(s):  
Rexiati Ruze ◽  
Qian Xu ◽  
Guoqin Liu ◽  
Yuekai Li ◽  
Weijie Chen ◽  
...  
Keyword(s):  
Cognitive Function ◽  
Glucose Uptake ◽  
Diabetic Rats ◽  
Brain Glucose ◽  
Positron Emission ◽  
Myosin Va ◽  
Glucagon Like Peptide 1 ◽  
Underlying Mechanisms ◽  
Related Proteins

The improvement of cognitive function following bariatric surgery has been highlighted, yet its underlying mechanisms remain elusive. Finding the improved brain glucose uptake of patients after Roux-en-Y gastric bypass (RYGB), duodenum-jejunum bypass (DJB) and sham surgery (Sham) were performed on obese and diabetic Wistar rats, and intracerebroventricular (ICV) injection of glucagon-like peptide-1 (GLP-1) analog liraglutide (Lira), antagonist exendin-(9-39) (Exe-9), and the viral-mediated GLP-1 receptor (Glp-1r) knockdown (KD) were applied on both groups to elucidate the role of GLP-1 in mediating cognitive function and brain glucose uptake assessed with the Morris water maze (MWM) and positron emission tomography (PET). Insulin and GLP-1 in serum and cerebral spinal fluid (CSF) were measured, and the expression of glucose uptake-related proteins including GLUT-1, GLUTT-4, pAS160, AS160, Rab10, Myosin-Va as well as the c-fos marker in the brain were examined. Along with augmented glucose homeostasis following DJB, central GLP-1 was correlated with the improved cognitive function and ameliorated brain glucose uptake, which was further confirmed by the enhancive role of Lira on both groups while the Exe-9 and Glp-1r KD were opposite. Known to activate insulin signaling pathways, central GLP-1 contributes to improved cognitive function and brain glucose uptake after DJB.

scholarly journals Depot-specific regulation of glucose uptake and insulin sensitivity in HIV-lipodystrophy

2006 ◽  
Vol 290 (2) ◽  
pp. E289-E298 ◽  
Author(s):  
C. Hadigan ◽  
D. Kamin ◽  
J. Liebau ◽  
S. Mazza ◽  
S. Barrow ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Uptake ◽  
Subcutaneous Fat ◽  
Fat Distribution ◽  
Whole Body ◽  
Glucose Disposal ◽  
Positron Emission ◽  
Specific Regulation ◽  
Hiv Lipodystrophy

Altered fat distribution is associated with insulin resistance in HIV, but little is known about regional glucose metabolism in fat and muscle depots in this patient population. The aim of the present study was to quantify regional fat, muscle, and whole body glucose disposal in HIV-infected men with lipoatrophy. Whole body glucose disposal was determined by hyperinsulinemic clamp technique (80 mU·m−2·min−1) in 6 HIV-infected men and 5 age/weight-matched healthy volunteers. Regional glucose uptake in muscle and subcutaneous (SAT) and visceral adipose tissue (VAT) was quantified in fasting and insulin-stimulated states using 2-deoxy-[18F]fluoro-d-glucose positron emission tomography. HIV-infected subjects with lipoatrophy had significantly increased glucose uptake into SAT (3.8 ± 0.4 vs. 2.3 ± 0.5 μmol·kg tissue−1·min−1, P < 0.05) in the fasted state. Glucose uptake into VAT did not differ between groups. VAT area was inversely related with whole body glucose disposal, insulin sensitivity, and muscle glucose uptake during insulin stimulation. VAT area was highly predictive of whole body glucose disposal ( r2 = 0.94, P < 0.0001). This may be mediated by adiponectin, which was significantly associated with VAT area ( r = −0.75, P = 0.008), and whole body glucose disposal ( r = 0.80, P = 0.003). This is the first study to directly demonstrate increased glucose uptake in subcutaneous fat of lipoatrophic patients, which may partially compensate for loss of SAT. Furthermore, we demonstrate a clear relationship between VAT and glucose metabolism in multiple fat and muscle depots, suggesting the critical importance of this depot in the regulation of glucose and highlighting the significant potential role of adiponectin in this process.

scholarly journals Effect of the glucagon-like peptide-1 receptor agonist lixisenatide on postprandial hepatic glucose metabolism in the conscious dog

2013 ◽  
Vol 305 (12) ◽  
pp. E1473-E1482 ◽  
Author(s):  
Mary Courtney Moore ◽  
Ulrich Werner ◽  
Marta S. Smith ◽  
Tiffany D. Farmer ◽  
Alan D. Cherrington
Keyword(s):  
Gastric Emptying ◽  
Glucose Uptake ◽  
Receptor Agonist ◽  
Area Under The Curve ◽  
Glucose Disposal ◽  
Saline Control ◽  
Valuable Adjunct ◽  
Hepatic Glucose ◽  
And Control ◽  
The Impact

The impact of the GLP-1 receptor agonist lixisenatide on postprandial glucose disposition was examined in conscious dogs to identify mechanisms for its improvement of meal tolerance in humans and examine the tissue disposition of meal-derived carbohydrate. Catheterization for measurement of hepatic balance occurred ≈16 days before study. After being fasted overnight, dogs received a subcutaneous injection of 1.5 μg/kg lixisenatide or vehicle (saline, control; n = 6/group). Thirty minutes later, they received an oral meal feeding (93.4 kJ; 19% protein, 71% glucose polymers, and 10% lipid). Acetaminophen was included in the meal in four control and five lixisenatide dogs for assessment of gastric emptying. Observations continued for 510 min; absorption was incomplete in lixisenatide at that point. The plasma acetaminophen area under the curve (AUC) in lixisenatide was 65% of that in control ( P < 0.05). Absorption of the meal began within 15 min in control but was delayed until ≈30–45 min in lixisenatide. Lixisenatide reduced ( P < 0.05) the postprandial arterial glucose AUC ≈54% and insulin AUC ≈44%. Net hepatic glucose uptake did not differ significantly between groups. Nonhepatic glucose uptake tended to be reduced by lixisenatide (6,151 ± 4,321 and 10,541 ± 1,854 μmol·kg−1·510 min−1 in lixisenatide and control, respectively; P = 0.09), but adjusted (for glucose and insulin concentrations) values did not differ (18.9 ± 3.8 and 19.6 ± 7.9 l·kg−1·pmol−1·l−1, lixisenatide and control, respectively; P = 0.94). Thus, lixisenatide delays gastric emptying, allowing more efficient disposal of the carbohydrate in the feeding without increasing liver glucose disposal. Lixisenatide could prove to be a valuable adjunct in treatment of postprandial hyperglycemia in impaired glucose tolerance or type 2 diabetes.

scholarly journals Obesity risk is associated with altered cerebral glucose metabolism and decreased μ-opioid and CB1 receptor availability

2021 ◽  
Author(s):  
Tatu Kantonen ◽  
Laura Pekkarinen ◽  
Tomi Karjalainen ◽  
Marco Bucci ◽  
Kari Kalliokoski ◽  
...  
Keyword(s):  
Risk Factors ◽  
Glucose Uptake ◽  
Familial Risk ◽  
Health Concern ◽  
Obesity Risk ◽  
Brain Glucose ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Familial Obesity ◽  
The Brain

Abstract Background Obesity is a pressing public health concern worldwide. Novel pharmacological means are urgently needed to combat the increase of obesity and accompanying type 2 diabetes (T2D). Although fully established obesity is associated with neuromolecular alterations and insulin resistance in the brain, potential obesity-promoting mechanisms in the central nervous system have remained elusive. In this triple-tracer positron emission tomography study, we investigated whether brain insulin signaling, μ-opioid receptors (MORs) and cannabinoid CB1 receptors (CB1Rs) are associated with risk for developing obesity. Methods Subjects were 41 young non-obese males with variable obesity risk profiles. Obesity risk was assessed by subjects’ physical exercise habits, body mass index and familial risk factors, including parental obesity and T2D. Brain glucose uptake was quantified with [18F]FDG during hyperinsulinemic euglycemic clamp, MORs were quantified with [11C]carfentanil and CB1Rs with [18F]FMPEP-d2. Results Subjects with higher obesity risk had globally increased insulin-stimulated brain glucose uptake (19 high-risk subjects versus 19 low-risk subjects), and familial obesity risk factors were associated with increased brain glucose uptake (38 subjects) but decreased availability of MORs (41 subjects) and CB1Rs (36 subjects). Conclusions These results suggest that the hereditary mechanisms promoting obesity may be partly mediated via insulin, opioid and endocannabinoid messaging systems in the brain.

scholarly journals The Effect of Sulphoraphane on Brain Glucose Uptake during Neonatal Hypoxic-Ischemic Encephalopathy in Newborn Rats

2021 ◽  
Vol 68 (1) ◽  
pp. 136-138
Author(s):  
S. Kapoor ◽  
D. Kala ◽  
J. Svoboda ◽  
Z. Brnoliakova ◽  
J. Otahal
Keyword(s):  
Glucose Uptake ◽  
Newborn Rats ◽  
Time Intervals ◽  
Brain Glucose ◽  
Positron Emission ◽  
Socioeconomic Burden ◽  
18F Fdg ◽  
Ischemic Encephalopathy ◽  
Present Pilot Study

Abstract Neonatal hypoxic-ischemic insult (HII) is one of the leading causes of morbidity and mortality in newborns. It has long-term consequences and represents a socioeconomic burden. It is an urgent issue in current neonatology. The aim of the present pilot study was to evaluate the possible effect of sulforaphane on brain glucose uptake expressed as 18F-fluorodeoxyglucose (18F-FDG) activity at the acute, subacute, and subchronic time intervals after the experimental perinatal HII in rats. Significant protection has been observed in the hippocampus 5 weeks after the insult as represented by normalisations of interhemispheric ratio of measured 18F-FDG activity. In conclusion, positron emission tomography (PET) with 18F-FDG revealed a protective effect of SFN on glucose metabolism in the subchronic phase after HII. Further research within the field of neonatal HII in newborn rats will be necessary.

Neural control of glucose uptake by skeletal muscle after central administration of NMDA

1995 ◽  
Vol 268 (2) ◽  
pp. R492-R497 ◽  
Author(s):  
C. H. Lang ◽  
M. Ajmal ◽  
A. G. Baillie
Keyword(s):  
Skeletal Muscle ◽  
Blood Flow ◽  
Glucose Uptake ◽  
Neural Control ◽  
Plasma Insulin ◽  
Regional Blood Flow ◽  
Muscle Blood Flow ◽  
Whole Body ◽  
Glucose Disposal ◽  
Central Administration

Intracerebroventricular injection of N-methyl-D-aspartate (NMDA) produces hyperglycemia and increases whole body glucose uptake. The purpose of the present study was to determine in rats which tissues are responsible for the elevated rate of glucose disposal. NMDA was injected intracerebroventricularly, and the glucose metabolic rate (Rg) was determined for individual tissues 20-60 min later using 2-deoxy-D-[U-14C]glucose. NMDA decreased Rg in skin, ileum, lung, and liver (30-35%) compared with time-matched control animals. In contrast, Rg in skeletal muscle and heart was increased 150-160%. This increased Rg was not due to an elevation in plasma insulin concentrations. In subsequent studies, the sciatic nerve in one leg was cut 4 h before injection of NMDA. NMDA increased Rg in the gastrocnemius (149%) and soleus (220%) in the innervated leg. However, Rg was not increased after NMDA in contralateral muscles from the denervated limb. Data from a third series of experiments indicated that the NMDA-induced increase in Rg by innervated muscle and its abolition in the denervated muscle were not due to changes in muscle blood flow. The results of the present study indicate that 1) central administration of NMDA increases whole body glucose uptake by preferentially stimulating glucose uptake by skeletal muscle, and 2) the enhanced glucose uptake by muscle is neurally mediated and independent of changes in either the plasma insulin concentration or regional blood flow.

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