Category Archives: biology

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.

What are hormones and how do they work: some basics

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.

Winter is coming and the basics of trade-offs in biology

Winter is coming and the basics of trade-offs in biology

Butterfly season is over and it’s getting cold out, although I did just see a cabbage white flapping around erratically when I was walking to work this morning. Despite the troubles we had early on in the summer with butterflies dying, we did manage to collect some good data. More importantly, I think that we worked most of the kinks out of our experimental design so next year should go much smoother. Now that I have the time, I’m going to sit down and try to explain my research project, and why I am doing it. The explanation will take 3 posts, so I can take my time explaining the concepts to interested folks who are not biologists.

One of the basic concepts underlying my research is that of a trade-off. A trade-off occurs when an organism wants to do two different things, but has a limited amount of some important resource. The resource could be time, calories, vital nutrients, or many other things. A simple example from everyday life would be trying to buy both a television and a bike with a limited amount of money. You can’t afford an expensive television AND an expensive bike. Instead, you have to choose between a cheap television and an expensive bike, a cheap bike and an expensive television, or a moderately priced bike and a moderately priced television. You would ideally want both an expensive bike and an expensive television, but you are limited by a resource: money.

Trade-offs in biology work similarly, but often the mechanism or the resource are not fully understood. This would be like seeing someone with a cheap bike and an expensive television, but not knowing WHY they have a cheap bike. You can guess that they have a cheap bike because they have limited money and want a nice television more than they want a nice bike, but you can’t know for sure. To biologists, this often takes the form of the observation that species rarely exhibit ‘perfect’ combinations of traits that are evolutionarily important, such as lifespan and reproductive rate. Some species, such as elephants, are very long lived, but reproduce very slowly (see Figure 1). Other species, such as mice, reproduce extremely rapidly, but are also short-lived. Slow reproduction with a short lifespan is clearly not a good strategy, and should generally not evolve. Conversely, an ideal combination from an evolutionary perspective would be to live a very long time and also have lots of kids really fast*.  Nevertheless, this is rarely seen in nature. Biologists generally agree that this pattern means that there is some cost to reproducing rapidly, and therefore species that reproduce rapidly will not live as long. There are many other examples of traits that are similar involved in trade-offs, such as brain size, muscle strength, and growth rate. Essentially, any trait that is important in fitness but requires some limited resource will likely exhibit trade-offs.

Reproduction and lifespan tradeoff more detail

The same patterns are generally seen within species as well, but individual trade-offs are often less consistent within species than they are among species. The specific ecological considerations of individual species may play a role, or it may be because there is simply more extreme variation among species compared to within species. In other species, some individuals may simply have access to more resources than others, meaning that despite the potential for a trade-off if resources are spread evenly across individuals, no trade-off is apparent due to inequalities among individuals. Someone who makes more money than you gets to have both an expensive television AND an expensive bike, avoiding the trade-off. In my next post I will talk about how hormones influence traits within species, and then finally I will bring together the ideas I’ve presented within the larger framework of my current research.

*There are some persuasive, but more complex considerations that I’m not covering here – for example in some cases longer-lived species may benefit disproportionately from intensive parental care, which may itself trade off with offspring number. However, the idea of a trade-off being responsible is widely accepted, and therefore I will not discuss these other possibilities further.