The Science of Insulin

One of the most powerful hormones in the human body, insulin doesn’t get the attention that it deserves most of the time and is unfortunately widely misunderstood. The obesity and diabetes frequency in the developed world is reaching epidemic proportions, and while there is a decent awareness of Type II diabetes and the lifestyle factors that are attributed to this, one of the main underlying causes that ties directly in is somehow not discussed as much as it should be1. In this article, we’ll examine what insulin is, its mechanisms, why insulin sensitivity is important and how to use it to your advantage in the world of sports nutrition.

Physiology of Insulin

Insulin was first discovered in 1889 by German scientists when it was hypothesized that a substance secreted by the pancreas was responsible for metabolic control, though at this time the exact substance and mechanism was unknown. It wasn’t until 1921 when in insulin was finally isolated, purified and available in a form capable of therapeutic administration and then further demonstrated that this extract lowered blood glucose and also restored hepatic glycogen mobilization and the capacity to clear ketones2.

In 1928, it was discovered that insulin was a polypeptide with an amino acid sequence that would be discovered much later in 1952. It has a chain comprising of 21 amino acids in the ‘A’ chain and 30 in the ‘B’ chain. Keeping these things in mind, in a simple explanation, insulin is secreted by the β cells of the pancreatic islets of Langerhans and maintains normal blood glucose levels by facilitating cellular glucose uptake, regulating carbohydrate, lipid and protein metabolism and promoting cell division and growth through its mitogenic effects3.

The synthesis and secretion of insulin is controlled by both nutrient and non-nutrient secretagogues. Nutrient secretagogues such as glucose trigger insulin secretion from the β cells by increasing intracellular ATP and closing of K+-ATP channels Insulin release appears to be further enhanced by the generation of cyclic AMP and other cellular energy intermediates. It is important to note that glucose doesn’t require insulin action to enter the β cell and start this process(nor do fructose, mannose or galactose)4. Non-nutrient secretagogues include neural stimuli such as cholinergic and adrenergic pathways, peptide hormones and cationic amino acids5.

Glucose Transporter Proteins

For glucose to enter the cells, Glucose Transporter Proteins (GLUT) come into play. There are various types of these GLUT and the characteristics vary depending on maximal glucose transport capability and insulin dependency (how much insulin is needed) based on the cells function6. There have been 5 subtypes identified thus far, with the one most pertinent to the world of sports nutrition generally being GLUT4 which is the one found in muscle and adipose tissue cells.

GLUT4 is the major glucose transporter protein, which requires insulin for its action and has a much higher Km for glucose. This enables adipose tissue cells, whose function is to store excess energy, to respond to the higher glucose levels characteristic of the fed state (vs fasted) and allows glucose to enter the cells where fatty acid and glycerol synthesis is stimulated and lipolysis suppressed temporarily. When glucose and insulin levels fall to fasting values, glucose no longer enters the cells, promoting lipolysis. In muscle cells, intracellular glucose transport facilitates glycogen synthesis…the crucial element for muscle building7!

Insulin Sensitivity

Now that we have covered a more in-depth area regarding physiology to understand insulin and its actions, an important factor that will be discussed in deep depth on a later article is insulin sensitivity. In a simple explanation, insulin resistance is believed to be caused at the cellular level via post-receptor defects in insulin signaling. While all the mechanisms are still being investigated, possible causes include down-regulation, deficiencies or genetic polymorphisms of tyrosine phosphorylation of the insulin receptor or may involve abnormalities of GLUT4 function.

This is an important issue especially in the world of improving body composition as insulin is anabolic in conjunction with growth hormone, IGF-1 and sufficient amino acids. It largely controls glycogen synthesis via activation of glycogen synthase which enables energy to be released anaerobically via glycolysis (e.g. during intense muscular activity). Insulin also is anabolic in it suppresses protein catabolism while insulin deficiency promotes it, releasing amino acids for gluconeogenesis. When the one is insulin resistant, muscle glycogen synthesis is impaired and this can also negatively affect protein synthesis6

Increasing Insulin Sensitivity: Exercise & Supplementation

When it comes to increasing insulin sensitivity, there are 2 main pathways that can be implemented. The first is though exercise and is considered to be the most potent stimulus to increase skeletal muscle GLUT4 expression in both healthy AND insulin resistant populations and a single bout of exercise can increase insulin sensitivity for up to 16 hours post exercise. It has also been shown to increase muscle GLUT4 protein content, elicit favorable changes in lipid metabolism and improve hepatic glucose output as well8. Exercise is also important as it has been shown in several studies that there is a link between higher amounts of body fat and lower insulin sensitivity9,10. It was observed at John Hopkins in a study that people with prediabetes who lost 5-7% of total body weight over the course of 6 months improved insulin sensitivity dramatically and reduced risk of type II diabetes by 54%11.

The second pathway that is pretty novel is that of supplementation. There have been several supplements that have shown promise in increasing insulin sensitivity including cinnamon, chromium, Banaba leaf, apple cider vinegar, etc. however the most promising one of the groups appears to berberine. Berberine is an alkaloid that has been used in traditional Chinese medicine is extracted from a variety of herbs. It works by activating an enzyme in the body called Adenosine Monophosphate-Activated Protein Kinase (AMPK)12. It also works to inhibit Protein Tyrosine Phosphatase 1B (PTP1B) and this combination of increasing AMPK and decreasing PTP1B leads to increased insulin sensitivity13. Berberine is a top choice as it has been shown in research that 1.5g of berberine can match the performance in regards to A1c-lowering effect of the prescription drug Metformin14. This is huge not only in that a naturally occurring alkaloid can go head to head with a pharmaceutical drug, but it also does so without the negative side effects that can be attributed to metformin.

The ‘gold standard’ in berberine for this purpose has traditionally been berberine HCL, however through research and advancements in science a more bioavailable version of berberine called dihydroberberine (DHB) has since been discovered with one such version being GlucoVantage from NNB Nutrition. DHB is one of the 17 metabolites of berberine and is incredibly powerful in it is the most bioavailable berberine available, being easily absorbed into the intestine where its then oxidized back into berberine and sent into the blood plasma15. This specific form of berberine was also shown in research in vitro to be five times the bioavailability of regular berberine. In reals world application this translates to a dose of 300mg instead of 1500mg which makes it much more cost effective and potent as well as easier on the stomach.

Conclusion: Insulin for the Win

             The goal of this article was to make you a little more familiar with what insulin is, how it works in the body and why maintaining sensitivity to this hormone is vital for a variety of reasons, both health and body composition related. When understood and used to your advantage, insulin can be one of the most powerful hormones in the body that can shape your physique in the way you want. To take advantage of it, keep insulin sensitivity high by exercising, keeping your body fat lower and utilize the latest science in supplementation. This three-pronged approach will have you reaching your goals and optimizing your health in no time and looking and performing better than ever while doing it!

References

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3.          Wilcox G. Insulin and Insulin Resistance. Clin Biochem Rev. 2005;26(2):19-39.

4.          Weiss M. Insulin Biosynthesis, Secretion, Structure, and Structure-Activity Relationships. EndoText. Published online 2000. www.endotext.org

5.          Alberti K. International Textbook of Diabetes Mellitus. 2nd ed. Chichester; 1997.

6.          Hunter S. Insulin action and insulin resistance: diseases involving defects in insulin receptors, signal transduction, and the glucose transport effector system. Am J Med. 1998;105(4):331-345. doi:10.1016/s0002-9343(98)00300-3

7.          Richter E. Exercise, GLUT4 and skeletal muscle glucose uptake. Physiol Rev. 2013;93(3):993-1017. doi:10.1152/physrev.00038.2012

8.          Borghouts L. Exercise and insulin sensitivity: a review. Int J Sports Med. 2000;21(1):1-12. doi:10.1055/s-2000-8847

9.          Hardy O. What causes the insulin resistance underlying obesity? Curr Opin Endocrinol Diabetes Obes. 2012;19(2):81-87. doi:10.1097/MED.0b013e3283514e13

10.        Mason C. Dietary weight loss and exercise effects on insulin resistance in postmenopausal women. Am J Prev Med. 2011;41(4):366-375. doi:10.1016/j.amepre.2011.06.042

11.        Maruthur N. Early Response to Preventive Strategies in the Diabetes Prevention Program. J Gen Intern Med. 2013;28(12):1629-1636. doi:10.1007/s11606-013-2548-4

12.        Lee Y. Berberine, a natural plant product, activates AMP-activated protein kinase with beneficial metabolic effects in diabetic and insulin-resistant states. Diabetes. 2006;55(8):2256-2264. doi:10.2337/db06-0006

13.        Chen C. Berberine inhibits PTP1B activity and mimics insulin action. Biochem Biophys Res Community. 2010;397(3):543-547. doi:10.1016/j.bbrc.2010.05.153

14.        Pang B. Application of Berberine on Treating Type 2 Diabetes Mellitus. Int J Endocrinol. 2015;905749. doi:10.1155/2015/905749

15.        Feng R, Shou J. Transforming berberine into its intestine-absorbable form by the gut microbiota. Sci Rep. 2015;5(12155). doi:10.1038/srep12155