Tag Archives: Insulin

What is insulin, and what does it actually do in our bodies?

Today I’m going to talk about another hormone, one that is really important both generally in biology, and clinically for many people: insulin.

Figure 1. Six insulin molecules bound together (called a hexamer)

Insulin is a peptide hormone, which means it’s a protein that circulates through our blood and allows different parts of our body to communicate with each other. Peptide hormones cause their effects by binding to partner proteins called receptors that sit on the outside (or across the membranes) of cells.

Insulin is produced by special cells in the pancreas called beta cells, and has many important effects effects in the body, although its most important effect is to regulate energy (sugar) intake into cells from blood.

Figure 2. Synthetic human insulin

Diabetes is probably the most well-known disease in which insulin is involved. People with type 1 diabetes lack the ability to produce insulin because their beta cells have been killed, usually by their own immune system. Type 2 diabetes is a little more complicated – generally years of overproduction of insulin lead the body to become ‘insulin resistant’. Insulin production decreases in many, and cells often respond inappropriately to insulin binding, releasing glucose instead of taking it up. Type 2 diabetes represents about 90% of diabetes cases (1).

Figure 3. Insulin signaling allowing glucose transport into the cell, where it is eventually stored as fat.

In healthy people, insulin concentrations increase in response to an increase in blood glucose. The rising insulin concentrations lead to cells taking up the glucose, stabilizing levels in the blood. Research suggests that the increased insulin concentrations increase Vmax (the maximum rate of glucose uptake), by providing additional transport sites across the cell membrane (2). After glucose is taking into cells, it is generally stored as either glycogen (in liver and muscle) to be used for easily accessible energy, or as fat for longer term storage (Figure 3).

Other animals have insulin too. Amazingly, insulin and its receptor are so similar among vertebrates that injecting insulin from chickens into humans has an even stronger effect on blood glucose than injecting human insulin. The same thing happens if you inject chicken insulin into fish, frogs, or mice (3). Both the insulin and insulin receptor genes are almost certainly homologous (evolved from the same ancestral gene) among vertebrates. Even insects and worms have insulin-like hormones that are very similar to ours, and many researchers think that these are homologous as well (for example references 4 and 5), making insulin-like peptides well over a billion years old (6).

References.

1. Rorsman, P. (2005) Review: Insulin secretion: function and therapy of pancreatic beta-cells in diabetes. British Journal of Diabetes and Vascular Disease 5 (4) 187-191.

2. Gottesman, I., Mandarino, L., Verdonk, C., Rizza, R., Gerich, J. (1982) Insulin increases the maximum velocity for glucose uptake without altering the Michaelis constant in man. Evidence that insulin increases glucose uptake merely by providing additional transport sites. J. Clin. Invest. 70 (6): 1310-4

3. Muggeo, M., Ginsberg, B.H., Roth, J., Neville, D.M., de Meyts, P., Kahn, C.R. (1979) The insulin receptor in vertebrates is functionally more conserved during evolution than insulin itself. Endocrinology. 104 (5)

4. Teleman, A.A. (2010) Molecular mechanisms of metabolic regulation by insulin in Drosophila. Biochem. J. 425 13-26.

5. Chistyakova, O.V. Signaling pathway of insulin and insulin-like growth factor-1 (IGF-1) as a potential regulator of lifespan. Journal of Evolutionary Biochemistry and Physiology 44 (1) 1-11

6. Wang, D.Y., Kumar, S., Hedges, S.B. (1999) Divergence time estimates for the early history of animal phyla and the origin of plants, animals and fungi. Proc. Biol. Sci. 266 (1415): 163-171

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A mitochondrial hormone that’s apparently a critical regulator of metabolism has been discovered

A new paper just came out in Cell Metabolism that is really cool for a couple reasons.

Lee et al. (2015) found that a hormone produced by mitochondria, parts of our cells that are important in metabolism and have their own DNA. They called the hormone MOTS-c.

Hormones, remember from earlier posts, are just signaling molecules that circulate in our cells and bodies and have important biological effects.

This discovery is especially cool for a couple reasons.

The first is that although we know that mitochondria are really important in metabolism, we don’t really know much about signaling molecules that are actually produced by our mitochondria.

The second is that the hormone appears to be really conserved among all mammals. This is often seen for hormones whose purpose is so specific, important, and widespread that its difficult for the hormone to even evolve. Insulin is another example of a hormone that is very conserved among mammals.

A final reason why this discovery is so cool is that MOTS-c seems to have really important effects on metabolism. It’s action activates AMPK. AMPK is another really important signaling molecule that we understand much more about. For now, its just important to know that AMPK regulates fat metabolism, and it looks like treatment with MOTS-c actually prevents obesity and insulin resistance in mice.

Maybe this represents a future treatment for obesity and diabetes? It’s actually quite strange to think that someday we might understand endocrinology well enough to regulate weight and even to some extent processes like aging by simply hormone injections without the current negative consequences that generally accompany these approaches.

That day is not yet here, so I’m gonna go hit the gym.

Lee, C., Zeng, J., Brew, B.G., Sallam, T., Martin-Montalvo, A., Wan, J., Kim, S., Mehta, H., Hevener, A.L., de Cabo, R., Cohen, P. (2015) The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 21, 443-454.