Proinsulin mRNA levels in fasting and fed ADX rats: evidence for an indirect effect of glucocorticoids

1989 ◽  
Vol 256 (2) ◽  
pp. E303-E308
Author(s):  
F. T. Fiedorek ◽  
M. A. Permutt
Keyword(s):  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Indirect Effect ◽  
Mrna Levels ◽  
Sucrose Intake ◽  
Dietary Manipulation ◽  
Glucose Levels ◽  
Mrna Concentration ◽  
Fasted Rats ◽  
Stimulation Of

To determine whether glucocorticoids are required to maintain pancreatic proinsulin mRNA levels during dietary manipulation, rats were adrenalectomized (ADX) or sham operated (SO) and subsequently fasted or pair fed for 2 days. Proinsulin mRNA concentrations were 54 +/- 8% lower (P less than 0.05) in fed ADX rats and 47 +/- 10% lower (P less than 0.01) in fasted ADX rats relative to values in fed and fasted SO rats, respectively. When ADX rats were fasted for 24 h and either refed 20% sucrose for 30 h or injected with dexamethasone (DEX) 0.125 mg/kg ip every 12 h for three doses, circulating plasma glucose levels were restored and pancreatic proinsulin mRNA concentrations rose 3.3 and 2.7-fold, respectively (each P less than 0.05). Plasma glucose and proinsulin mRNA levels (n = 40) were correlated (r = 0.58, P less than 0.0001). We conclude that the regulation of proinsulin mRNA concentration does not absolutely require endogenous glucocorticoids, since either adequate sucrose intake in ADX rats or physiological glucocorticoid responses in fasted rats suffice to restore pancreatic mRNA concentrations. It appears that glucocorticoid stimulation of pancreatic proinsulin mRNA levels is mediated indirectly through its regulation of glucose metabolism.

scholarly journals Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

1997 ◽  
Vol 17 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Naoaki Horinaka ◽  
Nicole Artz ◽  
Jane Jehle ◽  
Shinichi Takahashi ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
Insulin Hypoglycemia ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

Shivering thermogenesis and glucose uptake by muscles of normal or diabetic rats

1982 ◽  
Vol 242 (1) ◽  
pp. R109-R115 ◽  
Author(s):  
O. L. Smith ◽  
S. B. Davidson
Keyword(s):  
Glucose Uptake ◽  
Plasma Glucose ◽  
Serum Insulin ◽  
Liver Glycogen ◽  
Diabetic Rats ◽  
Glucose Levels ◽  
Severe Diabetes ◽  
Mild Diabetes ◽  
Fasted Rats ◽  
Shivering Thermogenesis

Acute cold exposure of normal rats (4 degrees C for 24 h) increased food intake, reduced plasma glucose and liver glycogen, caused a small increase in plasma free fatty acids, and lowered serum insulin concentration by 50%. In fasted rats, cold raised fatty acid levels twice as high as in fed. In mild diabetes (40 mg/kg streptozotocin iv) cold reduced glucose levels in blood and urine, but in severe diabetes (90 mg/kg) cold aggravated hyperglycemia and ketonuria. Changes in muscle glucose utilization were also studied, after evisceration (functional hepatectomy) of rats from each group. Uptake was calculated from the fall in plasma glucose concentration during the 4-h period after a load of 50% glucose iv. Cold normally increased uptake 67%, but it failed to do so in fasted rats. In diabetic rats, cold enhanced uptake, but only if the disease were mild or insulin controlled. Sensitivity of uptake to insulin was unaffected by cold. The results suggest that shivering thermogenesis, like exercise, can promote glucose uptake by skeletal muscle, if enough insulin is present to prevent excess mobilization of lipid substrates.

scholarly journals ChREBP-Knockout Mice Show Sucrose Intolerance and Fructose Malabsorption

2018 ◽  
Author(s):  
Takehiro Kato ◽  
Katsumi Iizuka ◽  
Ken Takao ◽  
Yukio Horikawa ◽  
Tadahiro Kitamura ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Knockout Mice ◽  
Gene Deletion ◽  
Body Weight Loss ◽  
Mrna Levels ◽  
Wild Type ◽  
Glucose Levels ◽  
Fructose Malabsorption ◽  
Sucrose Diet ◽  
Alpha Glucosidase

We have previously reported that 60% sucrose diet-fed ChREBP knockout mice (KO) showed body weight loss resulting in lethality. We aimed to elucidate whether sucrose and fructose metabolism are impaired in KO. Wild type mice (WT) and KO were fed a diet containing 30% sucrose with/without 0.08% miglitol, an α-glucosidase inhibitor, and these effects on phenotypes were tested. Furthermore, we compared metabolic changes of oral and peritoneal fructose injection. Thirty percent sucrose diet feeding did not affect phenotypes in KO. However, miglitol induced lethality in 30% sucrose-fed KO. Thirty percent sucrose plus miglitol diet-fed KO showed increased cecal contents, increased fecal lactate contents, increased growth of lactobacillales and Bifidobacterium and decreased growth of clostridium cluster XIVa. ChREBP gene deletion suppressed the mRNA levels of sucrose and fructose related genes. Next, oral fructose injection did not affect plasma glucose levels and liver fructose contents; however, intestinal sucrose and fructose related mRNA levels were increased only in WT. In contrast, peritoneal fructose injection increased plasma glucose levels in both mice; however, the hepatic fructose content in KO was much higher owing to decreased hepatic Khk mRNA expression. Taken together, KO showed sucrose intolerance and fructose malabsorption owing to decreased gene expression.

Cold exposure reverses inhibitory effects of fasting on peripheral glucose uptake in rats

1989 ◽  
Vol 257 (1) ◽  
pp. R96-R101 ◽  
Author(s):  
H. Shibata ◽  
F. Perusse ◽  
A. Vallerand ◽  
L. J. Bukowiecki
Keyword(s):  
Glucose Uptake ◽  
Cold Exposure ◽  
Plasma Glucose ◽  
Skeletal Muscles ◽  
Inhibitory Effects ◽  
Peripheral Tissues ◽  
Glucose Levels ◽  
Brown Adipose ◽  
Order Of Magnitude ◽  
Fasted Rats

The effects of fasting and cold exposure on glucose uptake in skeletal muscles (tibialis anterior, quadriceps, and soleus), heart, and brown adipose tissue (BAT) were studied in conscious rats. Glucose uptake was estimated by determining the glucose metabolic index of individual tissues using the 2-[3H]deoxyglucose method. Fasting for 18 h at 25 degrees C decreased plasma glucose levels (-40%) and glucose uptake in heart (-95%) and skeletal muscles (-64-90%) but did not significantly affect glucose uptake in BAT. Fasting for 48 h did not further decrease these parameters. On the other hand, cold exposure (48 h at 5 degrees C) of fed animals did not alter plasma glucose levels but increased glucose uptake in heart (73%), skeletal muscles (126-326%), and particularly in BAT (95-fold). Remarkably, cold exposure stimulated glucose uptake in BAT and skeletal muscles of 18-h fasted rats by the same order of magnitude as in fed animals (percentagewise), thereby indicating that glucose represents an essential metabolite for shivering (muscles) and nonshivering (BAT) thermogeneses. In the heart of starved animals, the cold-induced increase in glucose uptake was even more important (8-fold) than in fed animals. Considering that cold exposure of fasted rats results in a severe insulinopenia, it is suggested that cold exposure stimulates glucose uptake in peripheral tissues primarily by enhancing glucose oxidation via insulin-independent pathways.

scholarly journals Nighttime Administration of Nicotine Improves Hepatic Glucose Metabolism via the Hypothalamic Orexin System in Mice

Endocrinology ◽  
2016 ◽  
Vol 157 (1) ◽  
pp. 195-206 ◽  
Author(s):  
Hiroshi Tsuneki ◽  
Takashi Nagata ◽  
Mikio Fujita ◽  
Kanta Kon ◽  
Naizhen Wu ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Oral Intake ◽  
Mrna Levels ◽  
Active Period ◽  
Wild Type ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Deficient Mice

Abstract Nicotine is known to affect the metabolism of glucose; however, the underlying mechanism remains unclear. Therefore, we here investigated whether nicotine promoted the central regulation of glucose metabolism, which is closely linked to the circadian system. The oral intake of nicotine in drinking water, which mainly occurred during the nighttime active period, enhanced daily hypothalamic prepro-orexin gene expression and reduced hyperglycemia in type 2 diabetic db/db mice without affecting body weight, body fat content, and serum levels of insulin. Nicotine administered at the active period appears to be responsible for the effect on blood glucose, because nighttime but not daytime injections of nicotine lowered blood glucose levels in db/db mice. The chronic oral treatment with nicotine suppressed the mRNA levels of glucose-6-phosphatase, the rate-limiting enzyme of gluconeogenesis, in the liver of db/db and wild-type control mice. In the pyruvate tolerance test to evaluate hepatic gluconeogenic activity, the oral nicotine treatment moderately suppressed glucose elevations in normal mice and mice lacking dopamine receptors, whereas this effect was abolished in orexin-deficient mice and hepatic parasympathectomized mice. Under high-fat diet conditions, the oral intake of nicotine lowered blood glucose levels at the daytime resting period in wild-type, but not orexin-deficient, mice. These results indicated that the chronic daily administration of nicotine suppressed hepatic gluconeogenesis via the hypothalamic orexin-parasympathetic nervous system. Thus, the results of the present study may provide an insight into novel chronotherapy for type 2 diabetes that targets the central cholinergic and orexinergic systems.

Acute Effects of Central Neuropeptide Y Injection on Glucose Metabolism in Fasted Rats

1995 ◽  
Vol 89 (5) ◽  
pp. 543-548 ◽  
Author(s):  
J. P. H. Wilding ◽  
Y. T. Kruszynska ◽  
P. D. Lambert ◽  
S. R. Bloom
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Glucose Metabolism ◽  
Neuropeptide Y ◽  
Plasma Glucose ◽  
Hepatic Glucose Production ◽  
Constant Infusion ◽  
Initial Increase ◽  
Acute Effects ◽  
Fasted Rats

1. Neuropeptide Y is a potent appetite stimulant and has been found to modulate glucose metabolism when given chronically. The acute effects of neuropeptide on peripheral glucose handling have not been studied in detail. We have studied the acute effects of central nervous system injection of neuropeptide on glucose metabolism in vivo in the rat. 2. Rats implanted with chronic cannulae in the third cerebral ventricle were injected with either neuropeptide Y or saline and peripheral insulin sensitivity was assessed during a hyperinsulinaemic euglycaemic clamp. The effect of centrally injected neuropeptide Y on post-absorptive glucose metabolism was studied using a constant infusion of [6-3H]glucose. 3. Infusion of neuropeptide Y resulted in a 18% increase in glucose requirement during the clamp, suggesting increased peripheral tissue responsiveness to insulin. Neuropeptide Y injection in 10 h fasted rats increased plasma glucose (area under curve 9.9 ± 0.2 versus 9.1 ± 0.1 mmol h−1 I−1, P < 0.01), insulin (103 ± 23 versus 33 ± 8 pmol/l, P < 0.01, at 30 min) and glucagon (5.5 ± 0.5 versus 3.1 ± 0.3 pmol/l, P < 0.05, at 30 min). The increase in plasma glucose was due to an initial increase in the rate of appearance, which peaked between 20 and 30 min after neuropeptide Y infusion; over the entire 90 min 16% more glucose entered the systemic circulation in the neuropeptide Y-treated rats than in control rats, and the total quantity of glucose removed was also greater. 4. Neuropeptide Y in the central nervous system influences glucose metabolism by altering secretion of islet hormones, hepatic glucose production and the peripheral response to insulin.

scholarly journals Plasma Apolipoprotein E3 and Glucose Levels Are Associated in APOE ɛ3/ɛ4 Carriers

2021 ◽  
pp. 1-16
Author(s):  
Anna K. Edlund ◽  
Kewei Chen ◽  
Wendy Lee ◽  
Hillary Protas ◽  
Yi Su ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Test Scores ◽  
Plasma Insulin ◽  
Gray Matter Volume ◽  
Neuropsychological Test ◽  
Lower Plasma ◽  
Glucose Levels ◽  
Increased Risk ◽  
Plasma Apolipoprotein

Background: Altered cerebral glucose metabolism, especially prominent in APOE ɛ4 carriers, occurs years prior to symptoms in Alzheimer’s disease (AD). We recently found an association between a higher ratio of plasma apolipoprotein E4 (apoE4) over apoE3, and cerebral glucose hypometabolism in cognitively healthy APOE ɛ3/ɛ4 subjects. Plasma apoE does not cross the blood-brain barrier, hence we speculate that apoE is linked to peripheral glucose metabolism which is known to affect glucose metabolism in the brain. Objective: Explore potential associations between levels of plasma insulin and glucose with previously acquired plasma apoE, cerebral metabolic rate of glucose (CMRgl), gray matter volume, and neuropsychological test scores. Methods: Plasma insulin and glucose levels were determined by ELISA and a glucose oxidase assay whereas apoE levels were earlier quantified by mass-spectrometry in 128 cognitively healthy APOE ɛ3/ɛ4 subjects. Twenty-five study subjects had previously undergone FDG-PET and structural MRI. Results: Lower plasma apoE3 associated with higher plasma glucose but not insulin in male subjects and subjects with a body mass index above 25. Negative correlations were found between plasma glucose and CMRgl in the left prefrontal and bilateral occipital regions. These associations may have functional implications since glucose levels in turn were negatively associated with neuropsychological test scores. Conclusion: Plasma apoE3 but not apoE4 may be involved in insulin-independent processes governing plasma glucose levels. Higher plasma glucose, which negatively affects brain glucose metabolism, was associated with lower plasma apoE levels in APOE ɛ3/ɛ4 subjects. High plasma glucose and low apoE levels may be a hazardous combination leading to an increased risk of AD.

Role of nitric oxide in the regulation of glucose kinetics in response to endotoxin in dogs

2001 ◽  
Vol 91 (1) ◽  
pp. 130-136 ◽  
Author(s):  
H. S. Moeniralam ◽  
F. Sprangers ◽  
E. Endert ◽  
M. T. Ackermans ◽  
J. J. B. Van Lanschot ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
E Coli ◽  
Glucose Levels ◽  
High Doses ◽  
Glucose Plasma

The purpose of the present in vivo study was to determine the role of nitric oxide (NO) in the regulation of glucose metabolism in response to endotoxin by blocking NO synthesis with NG-monomethyl-l-arginine (l-NMMA). In five dogs, the appearance and disappearance rates of glucose (by infusion of [6,6-2H2]glucose), plasma glucose concentration, and plasma hormone concentrations were measured on five different occasions: saline infusion, endotoxin alone ( E coli, 1.0 μg/kg iv), and endotoxin administration plus three different doses of primed, continuous infusion of l-NMMA. Endotoxin increased rate of appearance of glucose from 13.7 ± 1.6 to 23.6 ± 3.3 μmol · kg−1· min−1( P < 0.05), rate of disappearance of glucose from 13.9 ± 1.1 to 24.8 ± 3.1 μmol · kg−1· min−1( P < 0.001), plasma lactate from 0.5 ± 0.1 to 1.7 ± 0.1 mmol/l ( P < 0.01), and counterregulatory hormone concentrations. l-NMMA did not affect the rise in rate of appearance and disappearance of glucose, plasma lactate, or the counterregulatory hormone response to endoxin. Plasma glucose levels were not affected by endotoxin with or withoutl-NMMA. In conclusion, in vivo inhibition of NO synthesis by high doses of l-NMMA does not affect glucose metabolism in response to endotoxin, indicating that NO is not a major mediator of glucose metabolism during endotoxemia in dogs.

scholarly journals Glucose Regulates Cyclin D2 Expression in Quiescent and Replicating Pancreatic β-Cells Through Glycolysis and Calcium Channels

Endocrinology ◽  
2011 ◽  
Vol 152 (7) ◽  
pp. 2589-2598 ◽  
Author(s):  
Seth J. Salpeter ◽  
Agnes Klochendler ◽  
Noa Weinberg-Corem ◽  
Shay Porat ◽  
Zvi Granot ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Division ◽  
Glucose Metabolism ◽  
Calcium Channels ◽  
Mrna Levels ◽  
Β Cells ◽  
Β Cell ◽  
Cyclin D2 ◽  
Glucose Levels

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G2-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication.

scholarly journals Central dopamine D2 receptors regulate plasma glucose levels in mice through autonomic nerves

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Hiroko Ikeda ◽  
Naomi Yonemochi ◽  
Risa Mikami ◽  
Manabu Abe ◽  
Meiko Kawamura ◽  
...  
Keyword(s):  
Glucose Level ◽  
Plasma Glucose ◽  
Receptor Agonist ◽  
Plasma Glucose Level ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Mrna Levels ◽  
Systemic Injection ◽  
Glucose Levels ◽  
Hepatic Glucose

AbstractRecent evidence suggests that the central nervous system (CNS) regulates plasma glucose levels, but the underlying mechanism is unclear. The present study investigated the role of dopaminergic function in the CNS in regulation of plasma glucose levels in mice. I.c.v. injection of neither the dopamine D1 receptor agonist SKF 38393 nor the antagonist SCH 23390 influenced plasma glucose levels. In contrast, i.c.v. injection of both the dopamine D2 receptor agonist quinpirole and the antagonist l-sulpiride increased plasma glucose levels. Hyperglycemia induced by quinpirole and l-sulpiride was absent in dopamine D2 receptor knockout mice. I.c.v. injection of quinpirole and l-sulpiride each increased mRNA levels of hepatic glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, which are the key enzymes for hepatic gluconeogenesis. Systemic injection of the β2 adrenoceptor antagonist ICI 118,551 inhibited hyperglycemia induced by l-sulpiride, but not by quinpirole. In contrast, hyperglycemia induced by quinpirole, but not by l-sulpiride, was inhibited by hepatic vagotomy. These results suggest that stimulation of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through parasympathetic nerves, whereas inhibition of central dopamine D2 receptors increases plasma glucose level by increasing hepatic glucose production through sympathetic nerves.

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