Presentation Title

The Mechanism by which Acute Hyperglycemia Alters Blood Flow Regulation in Skeletal Muscle

Faculty Mentor

Jeffery L Jasperse

Start Date

17-11-2018 8:30 AM

End Date

17-11-2018 10:30 AM

Location

CREVELING 98

Session

POSTER 1

Type of Presentation

Poster

Subject Area

biological_agricultural_sciences

Abstract

Endothelial cells contain nitric oxide synthase (NOS), an enzyme that produces nitric oxide (NO), a gas molecule that powerfully relaxes the neighboring smooth muscle cells causing dilation. Our lab sought to determine the mechanisms for potential vascular dysfunction caused by acute hyperglycemia. Hyperglycemia can increase the presence of reactive oxygen species (ROS), which can in turn reduce NO levels, thereby inhibiting arterial dilation. ROS are molecules that decrease NO bioavailability and cause tissue damage, including endothelial cells. Acute hyperglycemia could increase production of ROS through the activation of at least three different signaling pathways: 1) polyol pathway, 2) pentose-phosphate pathway (PPP), and 3) NADPH oxidase mechanism. In the polyol pathway, hyperglycemia leads to the increased production of the intermediate molecule, sorbitol, a sugar alcohol that attenuates NO production and leads to the increased production of constrictor substances including ROS that decrease arteries/arteriole diameter. Second, the pentose-phosphate pathway increases vasodilation by inhibiting the production of ROS. Third, an increase in activity and presence of the enzyme nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) increases the production of ROS which lead to cell damage and inhibits the activity of NOS, thus decreasing the bioavailability of NO. We hypothesized that the presence of high glucose will enhance the NADPH oxidase mechanism and polyol pathway while inhibiting the pentose-phosphate pathway. To test our hypothesis our lab conducted four experiments on two blood vessels, control and hyperglycemic (25mmol-L) soleus feed arteries (SFAs). The experiments served to identify the effects of hyperglycemia on certain elements. Our findings indicated that acute hyperglycemia attenuated dilation to acetylcholine (ACh) and constriction to phenylephrine (PE). The data suggest that hyperglycemia inhibits NO signaling pathways and causes an increase in the production of ROS which affects endothelial cell NOS. Additionally the PPP and the NADPH oxidase mechanism are activated during hyperglycemia and may be involved in the altered vascular responses.

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Nov 17th, 8:30 AM Nov 17th, 10:30 AM

The Mechanism by which Acute Hyperglycemia Alters Blood Flow Regulation in Skeletal Muscle

CREVELING 98

Endothelial cells contain nitric oxide synthase (NOS), an enzyme that produces nitric oxide (NO), a gas molecule that powerfully relaxes the neighboring smooth muscle cells causing dilation. Our lab sought to determine the mechanisms for potential vascular dysfunction caused by acute hyperglycemia. Hyperglycemia can increase the presence of reactive oxygen species (ROS), which can in turn reduce NO levels, thereby inhibiting arterial dilation. ROS are molecules that decrease NO bioavailability and cause tissue damage, including endothelial cells. Acute hyperglycemia could increase production of ROS through the activation of at least three different signaling pathways: 1) polyol pathway, 2) pentose-phosphate pathway (PPP), and 3) NADPH oxidase mechanism. In the polyol pathway, hyperglycemia leads to the increased production of the intermediate molecule, sorbitol, a sugar alcohol that attenuates NO production and leads to the increased production of constrictor substances including ROS that decrease arteries/arteriole diameter. Second, the pentose-phosphate pathway increases vasodilation by inhibiting the production of ROS. Third, an increase in activity and presence of the enzyme nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) increases the production of ROS which lead to cell damage and inhibits the activity of NOS, thus decreasing the bioavailability of NO. We hypothesized that the presence of high glucose will enhance the NADPH oxidase mechanism and polyol pathway while inhibiting the pentose-phosphate pathway. To test our hypothesis our lab conducted four experiments on two blood vessels, control and hyperglycemic (25mmol-L) soleus feed arteries (SFAs). The experiments served to identify the effects of hyperglycemia on certain elements. Our findings indicated that acute hyperglycemia attenuated dilation to acetylcholine (ACh) and constriction to phenylephrine (PE). The data suggest that hyperglycemia inhibits NO signaling pathways and causes an increase in the production of ROS which affects endothelial cell NOS. Additionally the PPP and the NADPH oxidase mechanism are activated during hyperglycemia and may be involved in the altered vascular responses.