Effects of Insulin on Endothelial Functions (SQ-5)
Researchers have long known that insulin resistance sets the stage for the development of Type 2 diabetes. Insulin resistance is a condition where beta cells of the pancreas produce insulin but muscle, liver and fat cells are not able to efficiently use it to absorb glucose from the bloodstream.
This leads to excessive build-up of glucose in the blood. As a result, the body gets signals to produce more insulin to take care of increased glucose levels until beta cells fails to keep up with this increased demand, finally leading to prediabetes and possibly Type 2 diabetes.
Increased levels of sugar and fats in the blood causes oxidative damage to blood vessels and encourages inflammation. The vascular endothelium (inner lining of blood vessels), responsible for carrying nutrients and macromolecules from blood to various tissues, is a major target of this oxidative stress.
That is why high glucose levels are found to create havoc on the vascular system – resulting in micro- and macro-vascular complications. For example, damage to large blood vessels triggers cardiovascular problems such as stroke and heart disease, and injury to small blood vessels – found in the eyes, kidneys and around nerves – and can lead to blindness, kidney failure and peripheral neuropathy that may even lead to limb amputations in severe cases.
At one point, as insulin resistance leads to high insulin levels circulating in the blood, it wasn't clear whether arteries become damaged because they are not able to respond to circulating insulin or because arteries get too much exposure. Studies now show that insulin resistance makes the arteries resistant too. Let’s take a look.
Insulin’s role in improving endothelial functions
We have known insulin as a hormone that promotes glucose uptake in liver, muscle and adipose tissue. But an extensive body of research suggests that insulin also helps in improving endothelial functions by stimulating the production of nitrous oxide (NO). Insulin signals complex pathways that involve activation of endothelial nitric-oxide synthase (eNOS), an enzyme that produces nitrous oxide.
NO is a potent vasodilator helping blood vessels to relax, especially in skeletal-muscle vascular beds. This mechanism serves to redistribute the postprandial (after-meal) blood flow, and along with it glucose and insulin, to the target tissues and organs. In other words, relaxed and dilated blood vessels allow for improved flow of blood and nutrients to skeletal muscle – resulting in efficient glucose disposal and suppression of insulin resistance. Insulin thus has a marked effect on vascular tone, by mediating nitric oxide production.
Insulin’s Role in Endothelial Health
- Promotes nitric oxide (NO) production, helping blood vessels relax
- Improves blood flow and nutrient delivery to skeletal muscle
- Supports glucose metabolism and reduces insulin resistance
- Enhances vascular tone and overall vascular health
Insulin resistance and reduced NO bioavailability: Effect on vascular health
In Type 2 diabetes, insulin resistance reduces bioavailability of Nitric oxide (NO). It leads to endothelial dysfunction and contributes to accelerated vascular diseases including hypertension, atherosclerosis, and coronary artery disease. In fact, many lines of evidence suggest that there exists an inverse relationship between insulin resistance and endothelial dysfunction [1, 2].A large number of studies also indicate that Nitric Oxide plays a larger role in supressing insulin resistance at various levels besides amplified delivery of glucose to peripheral tissues. For example, Nitric Oxide helps to reduce inflammation, increase production of free radicals in the mitochondria and prevent sticky blood vessels.
Nitric Oxide also plays a significant role in maintaining vascular health. According to a study “This protective molecule has a wide range of biological properties that maintain vascular homeostasis, including modulation of vascular dilator tone, regulation of local cell growth, and protection of the vessel from injurious consequences of platelets and cells circulating in blood, playing in this way a crucial role in the normal endothelial function.” [3]
It seems that enhancement of Nitric Oxide availability holds substantial promise in increasing endothelial functions for patients with insulin resistance and Type 2 diabetes.
Consequences of Insulin Resistance on Blood Vessels
- Reduced nitric oxide bioavailability
- Increased risk of hypertension and atherosclerosis
- Poorer vascular relaxation and increased stiffness
- Increased likelihood of cardiovascular issues and Type 2 diabetes complications
Vitamin C, Insulin sensitivity and Nitric Oxide availability
The good news is nutritional strategies and exercise regimens can help reverse blood-sugar fluctuations. Researchers believe that exercise may help in improving insulin resistance by making Nitric Oxide more bioavailable.
Vitamin C also has the ability to increase Nitric Oxide levels in the blood vessels and in turn improve endothelial functions as well as insulin sensitivity in patients suffering from Type 2 diabetes. A study shows that long-term treatment with Vitamin C, a nutrient that is also a super anti-oxidant, increases Nitric Oxide Synthases (NOSs) enzyme activity [4].
Vitamin C is also known to have beneficial effects in decreasing blood glucose and lipids levels in patients with Type 2 diabetes, reducing the risk of associated complications [5]. In addition, Vitamin C promotes the synthesis and repair of collagen in the connective tissue of endothelium – making the arterial walls strong and flexible and resisting the formation of plaque in the arteries.
Another interesting study shows that 500 mg/day supplementation of Vitamin C is as good in reducing blood vessels constriction as exercise [6]. The study shows that the blood vessels of overweight people have elevated activity of protein endothelin (ET)-1 that causes constrictions in small vessels, thus making blood vessels even more susceptible to constricting in such cases.
While regular exercise is known to reduce activity of the ET-1 protein, not many people are inspired to exercise often enough. Significantly, the research from the University of Colorado shows that supplementing with 500 mg Vitamin C daily could actually reduce ET-1 induced small vessel constriction as much as exercise.
However, please note that supplements can replace neither the plentiful nutrition you receive from a variety of foods nor the benefits of regular exercise. You should use these supplements as an integrative approach to boost the body’s capacity to restore balance and stay fit.
Read more about Liposomal Vitamin C
References:
- Kim J, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathphysiological mechanisms. Circulation 2006; 113: 1888-1904.
- Kim F, Pham M, Rizzo NO, Morton GJ, Wisse BE, Kirk EA, et al. Vascular inflammation, insulin resistance and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler Thromb Vasc Biol 2008; 28: 1982-1988.
- Tousoulis D et.al. The role of nitric oxide on endothelial function. Current Vascular Pharmacology. 2012 Jan;10(1):4-18.
- LV d’Uscio et. Al. Long-Term Vitamin C Treatment Increases Vascular Tetrahydrobiopterin Levels and Nitric Oxide Synthase Activity. Circulation Research. 2003
- Afkhami-Ardekani M, Shojaoddiny-Ardekani A. Effect of vitamin C on blood glucose, serum lipids & serum insulin in type 2 diabetes patients.The Indian Journal & Medical Research. 2007 Nov;126(5):471-4.
- Vitamin C: The Exercise Replacement? American Physiological Society. September 4, 2015.
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