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biology

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

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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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biology

What are hormones and how do they work: some basics

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We hear a lot about hormones these days. Estrogen is good for women; estrogen is bad for women. Growth hormone will help you stay young; growth hormone will give you cancer. Hormones make cows get big and tasty; hormones that we give cows are bad for our kids when they drink milk. But what IS a hormone? Why are they important? How do they work?

To start with, there are three major types of hormones – peptides, catecholamines, and steroids. Each one is different. But all three are released in response to a signal from the brain (or another hormone), and travel throughout your body in your blood, affecting cells and tissues along the way. Hormones are important before you are born, and until you die. They control how your body develops, and influence your behavior.

Peptides are proteins – they are produced within cells, and are represented by one gene. Insulin is a well-known example of a peptide hormone. Peptide hormones bind to receptors on the outside of cells, which results in complex signalling cascades (like a waterfall of biology inside the cell). These cascades eventually influence how DNA is turned into new proteins that will have different effects.

Catecholamines are kind of like amino acids, and function a little like peptides – binding to the outside of a cell. Epinephrine and dopamine are examples of catecholamines. Catecholamines can also be important in the brain.

Steroid hormones are the third major type of hormone, and perhaps the best known. Testosterone and estrogen are both examples of steroid hormones. Steroid hormones are similar in structure to cholesterol molecules, and in fact cholesterol is a kind of non-hormone steroid. Steroids differ from catecholamines and peptides in that they are able to enter cells. Instead of binding at cell surfaces, steroids can actually go straight to the DNA and have direct effects.

There are several more generally important things to recognize. First, the systems within cells that respond to hormones are very complex. Second, individuals vary genetically in how we produce hormones – your genes DO affect your life in many ways. Nevertheless, production of hormones from genes occurs in response to the environment – for example, insulin is produced in response to eating sugar. So what you do in life, what you think, and what you experience influences your hormones, which then influences your physical body. Hormonal systems are complicated and can affect each other. If you have a disorder that is characterized by low levels of a hormone, it can be difficult to figure out exactly what’s wrong – do you produce too little, does your body break it down extra fast, or is something else going on? Finally, there are other types of signals in our bodies – for example, ‘neurotransmitters’ work somewhat like hormones, but are in our brains. ‘Cytokines’ are another important signaling molecule that is especially common in immune function.

How hormones influence our outward traits, or ‘phenotypes’ is a complicated question, but hopefully this is enough of a background allowing readers without a background in biology to understand mention of hormones in future posts.