How does injected insulin work?

I’ve recently started taking insulin (both fast-acting and long-acting) and while they explained what it does, they really didn’t get into the mechanics of how it gets to where it’s supposed to go.

This is actually two questions, I guess. The first is, when I inject, I inject at one site, usually on my abdomen. How does that insulin, all of which is at one little point under my skin, get to where it needs to go? It’s not intravenous, so it’s not traveling by the body’s “highways”. It’s just injected intradermally, into the fat layer underneath. So how does it get to all of my cells to play doorman for that sweet, sweet glucose?

Second question would be, how does the long-acting insulin work differently than the short-acting? Does that little (well, not so little for the long-acting) bolus of insulin sit there and gradually disperse in some way? Or does it immediately disperse just like the short-acting, but “hang around” the cells for longer due to some mechanism?


I’m sure someone who knows more about it that I do will come along soon enough, but my understanding is that you don’t need to get it to a vein to get the blood to carry it throughout the body, getting it into the fatty tissue below your skin allows capillary action to do the rest.

Long-acting dispersion differs depending on what you’re on.

From Using Insulin:

You actually don’t want it going into a vein, because it will work too fast. You’re supposed to stick the needle in and pull it back a bit to see if you get blood into the syringe, and if you do, you’re supposed to choose another site. I don’t know of anyone who actually does this, though.

We use different kinds of insulin to more closely mimic the blood sugar control of a person without diabetes. Our bodies produce and release some insulin all the time, and more at meals. When your doctor gives you one long acting insulin, that mimics the “all the time” insulin, and the rapid-acting or regular insulin are the “more at meals” insulin. We call the “more at meals” (or at other times when your blood sugar is high) a “bolus”. Just means “extra”, really.

Insulin is a hormone - a protein - which moves from your fat into your blood through tiny holes in the capillary walls, and then throughout the body, where it leaves through tiny holes in the capillary walls.

In an emergency, a person **can **be given insulin straight into their vein through an IV, but you run the risk of lowering their blood sugar too much or too fast, causing hypoglycemia. Hypoglycemia can cause Really Bad Things, including coma and seizures, so IV insulin is pretty rare, even in hospitals. By using insulin subcutaneously - into the fat pad under your skin - it releases at a much slower and more gradual rate, and is far easier to control without making you hypoglycemic.

Regular insulin takes about 30 minutes to an hour to get to all your cells, which is why you often inject it before you make your meal. Rapid acting insulin takes only 15 minutes to get to all your cells, which is why you don’t inject it until you have food on the table in front of you. If you take it and don’t eat, you may become dangerously hypoglycemic.

Long acting insulin takes, on average, 1-3 hours to begin to get to all your cells, so you don’t have to worry about timing it to your food. Rather, you take it at the same time every day.

There are three ways in which regular insulin is changed into long acting insulin. All of these are designed to slow down the absorption step.

  1. Lente crystalline zinc insulin (Ultralente, NPH or Lente insulines). They add zinc to the insulin. This zinc affects the chemical structure so that the insulin breaks down a bit (into dimers and hexamers - smaller chemical chains) at the site of injection, and that makes it absorb more slowly into your system.

  2. Insulin glargine. This is an insulin molecule that, with recombinant DNA technology, has had 2 arganine molecules attached in one spot and one asparagine molecule taken out and replaced with a glycine. So it’s not exactly insulin anymore, and we call in an “insulin analogue”. It acts like insulin where we want it to, but it’s got a more neutral pH. More neutral pH means that it’s absorbed out of your injection site more slowly.

  3. Insulin detemir (Levemir). This is an insulin molecule that has a fatty acyl chain bonded to it. Again, this changes the molecule, so we can’t call it “insulin” anymore; it’s another insulin analogue. This fatty acly chain makes it attach itself to the albumin in your body. Albumin is a protein in your blood and on your cells. The insulin detemir attaches to it and then peels away slowly, again slowing the time it takes to get fully absorbed.

Other chemical changes are made to insulin to make rapid acting insulin analogues, like Lispro and Aspart. But since you didn’t ask about them, I’m going to skip the chemistry. :wink: Suffice it to say that those chemical changes make the insulin analogues absorb more quickly than regular insulin. That makes it good for meal coverage, but not effective for long term glucose control. If you used just rapid acting insulin, your blood glucose level would yo-yo all day, and that’s not what we want. That way lies peripheral vascular disease and amputations.

The current standard of practice is to use both a long term and a bolus of regular or rapid acting insulin in the amount they’re needed in order to keep the patient’s blood glucose as even and close to 100 as possible.

That’s not 100% correct - you can use rapid acting as basal insulin in place of long-acting. That’s what pumps do. It’s just that you wouldn’t want to do it without a pump, since you probably don’t want to give yourself injections every few seconds the way the pumps do it.

Yes, of course. I should have been clearer that I meant, “if you injected only rapid acting insulin with a syringe” i.e. without a pump. I don’t know enough about pumps to teach about them yet. Thank you for that clarification.

Did the rest seem okay? I’m trying not to use obnoxious medicalese.

Sounded good to me!

Though this made me laugh:

I’ve been diabetic long enough now that “as even and close to 100” just makes me break out in hysterical giggles. I’m sure others can relate!

Oh, I know. If it makes you feel any better, though, more recent research is suggesting that super-tight glycemic control may not actually be as important as we make it out to be right now. That there’s not an actual medical benefit, and it might just drive patients to stab us to death with sporks. :wink: Of course, they’re preliminary studies, so only time will tell. For now though, I’ve still got to emphasize tight control because it’s the most supported by the evidence at this time.

I’m a Type II diabetic, though not (yet, anyway) needing to take insulin. Nonetheless, I found your post to be very interesting and informative, and not difficult to follow in the slightest. Thanks for posting it!

Absolutely, WhyNot! Very clear. Thank you and everyone else who answered…it really helped me understand what’s going on with all the stuff that’s going on, so to speak.

Yay! Awesome, glad I could help. I admit, I used it as an excuse to review insulins for my upcoming nursing license test. :wink:

Well, glad I could help you, then! :slight_smile:

I’m not really newly diagnosed, but I have been for a number of years poorly controlled, mostly because I kept trying to keep doing things (diet, exercise, etc) the old way and hoping my oral medication would magically take care of everything (I’m on metformin right now, along with the Lantus and Humalog). My last blood labs convinced me I was playing Russian Roulette with three chambers loaded (pretty much an exact quote from my doc), so I’m currently in the middle of diabetic living classes. This is “management week” (last week was “nutrition week”), and we had a long discussion of the types of insulin that are available, but didn’t get into the actual nuts & bolts of what goes on at the cellular-to-molecular level.

ETA: And good luck on the licensing!

I’m glad you’ve seen the light. It would be really hard to post on the Dope with all your fingers amputated, my dear, and I’d miss you. :slight_smile:

Very good explanation, really nothing for me to add, and you did the explanation using laymen terms. You’re going to be a great nurse one day.

However, there is a “slight” nitpick,

You explained what makes Lantus different correctly, however, the conclusion is wrong. I hate to use that word, “wrong”, since it is a good explanation in laymen terms, but since this is GQ, I’m allowed to be nit-picky right?

The change of the amino acids help to stabilize the hexamer configuration, which keeps the lantus molecule from acting on the insulin receptors, until it changes into the monomer form. The actual molecule is still absorbed into circulation, it just doesn’t do anything while it is there.

But, the way you explained it is better for a patient who isn’t a pharmacist or a chemist :smiley:

Good luck with the Insulin. I’ve certainly found that for me, at least, it’s a great drug. Once you get beyond Metformin for Type 2, it seemed to me that all the others were scary in various ways (Sulfonylureas because they can make you go low, Byetta, Januvia, and others because they haven’t been around very long, etc. etc.) Insulin works really well, has been around for a long time, and really has only one potential side effect - make a mistake, you go low. I’d already started on my plot to make the docs give me Insulin when they thought I was Type 2, and once they decided I was Type 1 I was thrilled. Well, as thrilled as one could be, given the circumstances.

I loved byetta, until it started making me lose foods … I still have trouble with pork and nausea, though I can eat bacon, maybe 2 strips before the idea of bacon makes me nauseated, breakfast sausage makes me want to hurl still =( I have hope, I can eat beef in all forms, chicken in all forms, eggs again finally.

Absolutely, pick away at those nits! I will amend my notes, since this wasn’t really explained in class well at all. So it does slow the breakdown into the active form of insulin, but it doesn’t slow absorption from the injection site? Is that right?

Since we’re picking at nits…you mentioned that IV insulin is rarely used, even in hospitals. On my unit I don’t think a day goes by where there is at least one diabetic soul getting IV (regular) insulin. Granted, they are relatively sick (DKA), but yeah, IV insulin is not at all uncommon.

Anyway, best of luck to you, WhyNot - you’re going to be great at patient education. :smiley:

Huh. I haven’t seen it yet. What unit do you work in? I haven’t spent oodles of time in ER or ICU where the DKA patients would likely be, I’ve been mostly Med-Surg and Cardiac/Telemetry. When I asked the nurses up there, most of them haven’t *ever *hung IV insulin; it’s truly “rarely” in comparison to regular insulin, which they hand out like injectible Tic-Tacs. Maybe they move the patients off the regular floor if they need IV insulin because they need closer monitoring?

I’m a vetico-in-training, not a medico, but I’ll take a stab at the IV vs SQ thing. If a person/animal/vegetable/mineral is well-controlled on an insulin regimen, or if you are creating an insulin regimen for them to go home on, you would want to use the same dose and route they use at home - there’s no reason to change, IV insulin isn’t going to mimic their normal curves at home, and as noted above it requires tighter regulation. I wouldn’t be surprised if anyone who needed IV insulin were in or on the way (ER) to the ICU.

When you want IV insulin is when the situation is changing rapidly, there’s a greater need for insulin than normal, and you want the insulin to act very rapidly and go away rapidly if you stop. Also, in situations where peripheral perfusion is lousy, absorption from a SQ site might not be as reliable. In a patient with DKA, you need to bring their glucose down by a lot, fairly rapidly, without overshooting, so having a titratable (or however you spell that) drip allows you to do so safely without waiting for absorption and possibly giving too much. Ditto for patients with severe sepsis, acute liver failure, etc. - they may not even be diabetic normally, and you don’t really know how their body is going to react given all of the metabolic fluctuations happening. IV insulin w/dextrose can also be part of treating severe hyperkalemia.

BTW, I’m not familiar with the literature re: long-term control, but my understanding of glycemic control in the critical care setting is that, while some subgroups of patients might benefit, tight glycemic control might even be harmful in some cases and so strict control with a goal of 100 or even 110 is usually contraindicated. Here is a consensus statement from several endocrinology groups.