Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats☆
Section snippets
Animals
Male Sprague-Dawley rats (weight, 200 to 220 g; Taconic Farms, Germantown, NY) were acclimated in individual cages in a light-controlled room (12 hours on/12 hours off) at 22 to 24°C for 4 days in the animal facility of Beth Israel Deaconess Medical Center. During this period, animals were given free access to food and tap water. The laboratory diet contained 24 % protein, 6 % fat, and 4.5 % fiber with adequate minerals and vitamins (Rodent diet 8664, Harlan Teklad, Madison, WI).
After
Results
At the onset of the experiment, serum glucose was similar in all animals while insulin was not determined because of the limited blood sample from the tail vein. During the experiment, serum glucose concentrations were maintained at basal levels (110 ± 9 mg/dL) in both the Con and Surg − clamp groups. However, in the Surg + clamp group glucose level was significantly raised to 350 mg/dL and effectively maintained by glucose infusion. At the end of the study, serum insulin levels were
Discussion
In this study, the hyperglycemic clamp technique was used to achieve an elevated glucose (∼350 mg/dL) level for 3 hours, and the effects of this level of blood glucose on activation of systemic inflammation and development of oxidative stress were assessed. An average 0.09 g of glucose/kg/min was infused into animals, which would provide approximately 460 calories/kg/d if continued at this rate. This amount of energy intake is about 2.5 times the required energy for rats of this size (estimated
References (35)
Update on total parenteral nutrition
Am J Clin Nutr
(2001)Total parenteral nutritionPotion or poison?
Am J Clin Nutr
(2001)- et al.
Molecular mechanisms of tumor necrosis factor alpha gene expression in monocytic cells via hyperglycemia-induced oxidant stress-dependent and -independent pathways
J Biol Chem
(2000) - et al.
Indices of lipid peroxidation in vivoStrengths and limitations
Free Radic Biol Med
(2000) - et al.
Rapid activation and nuclear translocation of mitogen-activated protein kinases in response to physiological concentration of glucose in the MIN6 pancreatic beta cell line
J Biol Chem
(1998) - et al.
Effect of glucose on stress-activated protein kinase activity in mesangial cells and diabetic glomeruli
Kidney Int
(1999) - et al.
Abnormalities in protein kinase C and MAP kinase cascade in mesangial cells cultured under high glucose conditions
J Diabetes Compl
(1995) - et al.
Hyperglycemia enhances angiotensin II-induced janus-activated kinase/STAT signaling in vascular smooth muscle cells
J Biol Chem
(1999) - et al.
Effects of parenteral nutrition supplemented with glutamine or glutamine dipeptides on liver antioxidant and detoxification systems in rats
Nutrition
(2000) - et al.
Resting energy expenditure in the critically illEstimations versus measurement
Br J Surg
(1988)
Hyperglycemia associated with high, continuous infusion rates of total parenteral nutrition dextrose
Nutr Clin Pract
Intensive insulin therapy in critically ill patients
N Engl J Med
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nature
Hyperglycemia-induced activation of nuclear transcription factor kappaB in vascular smooth muscle cells
Diabetes
Infections and diabetesMechanisms and prospects for prevention
Diabet Med
Immunologic effects of acute hyperglycemia in nondiabetic rats
JPEN J Parenter Enteral Nutr
Inhibition of IL-6-activated janus/signal transducers and activators of transcription but not mitogen-activated protein kinase signaling in liver of endotoxin-teated rats
Crit Care Med
Cited by (64)
Hyperglycemia induces embryopathy, even in the absence of systemic maternal diabetes: An in vivo test of the fuel mediated teratogenesis hypothesis
2014, Reproductive ToxicologyCitation Excerpt :There are two conventional in vivo approaches to testing the fuel mediated teratogenesis hypothesis: (i) induction of diabetes in the pregnant rodent by various means such as streptozotocin [47], (ii) systemic administration of glucose [24,48]. However, neither of these approaches allows analysis of the isolated local effects of individual fuels on diabetic embryopathy because (i) systemic diabetes induces multifaceted irregularities in the maternal circulation, including abnormal energy fuels, inflammation, and oxidative stress, as noted in the introduction, and (ii) systemic induction of hyperglycemia by glucose administration produces a myriad of rapid (within hours) systemic aberrations including increased plasma triglycerides [25], oxidative stress and systemic inflammation [28–30], altered insulinemia [49], altered gene expression in tissues [50], and altered lipid and amino acid metabolism [26,27]. One elegant in vivo study tested whether hyperglycemia is necessary to induce diabetes-related embryopathy by treating diabetic pregnant rodents with phlorizin to selectively ameliorate the hyperglycemia but not the insulinopenic state [24].
The manner of the inflammation-boosting effect caused by acute hyperglycemia secondary to overfeeding and the effects of insulin therapy in a rat model of sepsis
2013, Journal of Surgical ResearchCitation Excerpt :The second key question is whether insulin therapy can inhibit such an inflammation-boosting effect caused by acute hyperglycemia. The third key question is whether insulin therapy also improves metabolic stress associated with acute hyperglycemia induced by overfeeding, such as the oxidative stress [9,11]. To examine these issues, we designed a rat model of acute hyperglycemia obtained by adjusting intravenous glucose loading under septic conditions induced by cecal ligation and puncture (CLP).
Hesperidin and naringin attenuate hyperglycemia-mediated oxidative stress and proinflammatory cytokine production in high fat fed/streptozotocin-induced type 2 diabetic rats
2012, Journal of Diabetes and its ComplicationsCitation Excerpt :Liver is the focal organ of oxidative and detoxifying processes as well as free radical reactions and the biomarkers of oxidative stress are elevated in the liver at an early stage in many diseases, including diabetes mellitus (Stadler, Jenei, von Bölcsházy, Somogyi, & Jakus, 2003). In experimental diabetes, STZ exerts its toxic effect on liver and other organs in addition to pancreatic β-cells (Ling, Mueller, Smith, & Bistrian, 2003). The insulin insufficiency and hyperglycemia that result from β-cell necrosis further augment liver damage through ROS-mediated lipid peroxidation of hepatocellular membrane (Kume et al., 2004).
The antidiabetic effect of garlic oil is associated with ameliorated oxidative stress but not ameliorated level of pro-inflammatory cytokines in skeletal muscle of streptozotocin-induced diabetic rats
2012, Journal of Traditional and Complementary Medicine
- ☆
Supported in part by National Institutes of Health Grant No. DK 50411 (R.J.S., P.R.L. and B.R.S.)