No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans.

Hasselbalch, Steen G.; Knudsen, Gitte M.; Videbæk, Charlotte; Pinborg, Lars H.; Schmidt, J. F.; Holm, Søren; Paulson, Olaf B.

doi:10.2337/diabetes.48.10.1915

Cited by 148 publications

(124 citation statements)

References 11 publications

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“…Insulin crosses the blood-brain barrier via the saturable transport system (19). Some studies in subjects with normal glucose tolerance have failed to show any effect of insulin on brain glucose metabolism (20), whereas other studies have demonstrated that insulin increases CMR glu (21). However, in our study, the rise in plasma insulin and glucose concentrations after EX was reduced compared with PLC, making this an unlikely explanation for the increase in CMR glu .…”

Section: Discussioncontrasting

confidence: 73%

Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System

et al. 2015

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Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA 1c of 5.7 6 0.1%, fasting glucose of 114 6 3 mg/dL, and 2-h glucose of 177 6 11 mg/dL, exenatide (5 mg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMR glu ) was measured by positron emission tomography after an injection of [ 18 F]2-fluoro-2-deoxy-D-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO 0-60 min (4.6 6 1.4 vs. 13.1 6 1.7 mmol/min $ kg) and decreased the rise in mean glucose 0-60 min (107 6 6 vs. 138 6 8 mg/dL) and insulin 0-60 min (17.3 6 3.1 vs. 24.7 6 3.8 mU/L). Exenatide increased CMR glu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO 0-60 min after exenatide was inversely correlated to CMR glu . In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.

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Section: Discussioncontrasting

confidence: 73%

Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System

et al. 2015

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“…Indeed, besides results in various tissues showing an SUV overestimation, Minamimoto et al reported a small but significant decrease of 18 F-FDG accumulation in the brains of patients with suspected renal failure, compared with healthy volunteers (11). Although the relationship between kidney disease and insulin resistance of the brain is not known, these authors discussed this particular result with the results of other investigators studying diabetes (12,13).…”

Section: Discussionmentioning

confidence: 85%

The Effect of Renal Failure on 18F-FDG Uptake: A Theoretic Assessment

Laffon

Cazeau²,

Monet³

et al. 2008

Journal of Nuclear Medicine Technology

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This work addresses the issue of using 18 F-FDG PET in patients with renal failure. Methods: A model analysis has been developed to compare tissue 18 F-FDG uptake in a patient who has normal renal function with uptake in a theoretic limiting case that assumes tracer plasma decay is tracer physical decay and is trapped irreversibly. Results: This comparison has allowed us to propose, in the limiting case, that the usually injected activity be lowered by a factor of 3. We also proposed that the PET static acquisition be obtained at about 160 min after tracer injection. These 2 proposals were aimed at obtaining a similar patient radiation dose and similar tissue 18 F-FDG uptake. Conclusion: In patients with arbitrary renal failure (i.e., between the 2 extremes of normal function and the theoretic limiting case), we propose that the injected activity be lowered (without exceeding a factor of 3) and that the acquisition be started between 45 and 160 min after tracer injection, depending on the severity of renal failure. Furthermore, the model also shows that the more severe the renal failure is, the more overestimated is the standardized uptake value, unless the renal failure indirectly impairs tissue sensitivity to insulin and hence glucose metabolism.

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“…steroid action. These are all areas, specifically the paraventricular nucleus of the hypothalamus (13), the ventromedial hypothalamus (11,17,24), and the hindbrain (34), that have been implicated in regulating counterregulatory responses to hypoglycemia and contain E2 and P4 receptors. Central injections of E2 into hindbrain areas have been found to depress renal sympathetic drive and increase vagal nerve activity in male rats (30,32).…”

Section: Discussionmentioning

confidence: 99%

Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

Sandoval¹,

Gong²

2007

American Journal of Physiology-Endocrinology and Metabolism

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aim of this study was to test the hypothesis that antecedent short-term administration of estradiol or progesterone into the central nervous system (CNS) reduces levels of neuroendocrine counterregulatory hormones during subsequent hypoglycemia. Conscious unrestrained male Sprague-Dawley rats were studied during randomized 2-day experiments. Day 1 consisted of an 8-h lateral ventricle infusion of estradiol (1 g/l; n ϭ 9), progesterone (1 g/l; n ϭ 9), or saline (0.2 l/min; n ϭ 10). On day 2, a 2-h hyperinsulinemic (30 pmol ⅐ kg Ϫ1 ⅐ min Ϫ1 ) hypoglycemic (2.9 Ϯ 0.2 mM) clamp was performed on all rats. Central administration of estradiol on day 1 resulted in significantly lower plasma epinephrine levels during hypoglycemia compared with saline, whereas central administration of progesterone resulted in increased levels of plasma norepinephrine and decreased levels of corticosterone both at baseline and during hypoglycemia. Glucagon responses during hypoglycemia were unaffected by prior administration of estradiol or progesterone. Endogenous glucose production following day 1 estradiol was significantly lower during day 2 hypoglycemia, and consequently, the glucose infusion rate to maintain the glycemia was significantly greater after estradiol administration compared with saline. These data suggest that 1) CNS administration of both female reproductive hormones can have rapid effects in modulating levels of counterregulatory hormones during subsequent hypoglycemia in conscious male rats, 2) forebrain administration of reproductive hormones can significantly reduce pituitary adrenal and sympathetic nervous system drive during hypoglycemia, 3) reproductive steroid hormones produce differential effects on sympathetic nervous system activity during hypoglycemia, and 4) reduction of epinephrine resulted in significantly blunted metabolic counterregulatory responses during hypoglycemia. epinephrine; sex differences; reproductive hormones WOMEN, COMPARED WITH MEN, have reduced autonomic responses to psychological stress (22), exercise (8,19,40), and hypoglycemia (14). We have previously shown that women taking estrogen replacement therapy have reduced autonomic counterregulatory activity in response to insulin-induced hypoglycemia compared with age-and body mass index-matched men and women not taking estrogen replacement therapy (35), thus suggesting that chronic elevations in estradiol may be an important mechanism for sexually dimorphic responses to stress.Previous studies have demonstrated that estrogen can have rapid biological effects in the brain and periphery (15,25,31,41). Whether these rapid effects are mediated through the classical estrogen receptors (estrogen receptor-␣ and/or -␤) or nongenomic mechanisms is not understood. In vitro estradiol increases intracellular signaling within minutes (23). In vivo, both centrally and peripherally administered estrogen increases intracellular signaling within the hypothalamus at 6 and 24 h after injection. These signaling changes may mediate a variety of physiological c...

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No effect of insulin on glucose blood-brain barrier transport and cerebral metabolism in humans.

Cited by 148 publications

References 11 publications

Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System

Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System

The Effect of Renal Failure on 18F-FDG Uptake: A Theoretic Assessment

Antecedent short-term central nervous system administration of estrogen and progesterone alters counterregulatory responses to hypoglycemia in conscious male rats

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