fat kills beta cells

How Fat Kills Insulin-Producing Beta Cells: A Lesson for Those With and Without Diabetes

An overwhelming amount of scientific evidence shows that a high-fat diet is the single most effective method at inducing insulin resistance in both your liver and muscle. This research clearly demonstrates that increasing dietary fat intake has an immediate negative effect on insulin sensitivity, which can then develop into a chronic state of insulin resistance and diabetes if the quantity of dietary fat remains high (1–26). For more information on this topic, read What Causes Insulin Resistance? Lipid Overload and The 3 Causes of Insulin Resistance in Type 1 Diabetes, Type 2 Diabetes and Prediabetes. Many people ask me about the specific mechanism how fat can destroy insulin-producing beta cells. Let’s explore beta cell stress in detail.

What are Beta Cells and Why are They Important?

The insulin producing beta cells in your pancreas are highly specialized cells because they are the only cell type that can make insulin. Jeopardizing insulin production results in severe metabolic problems that can then lead to whole-body organ dysfunction and eventually death. Because of this, protecting beta cell health throughout life is crucial for long-term health.

What Causes Beta Cell Dysfunction?

In the same way that your liver and muscle accumulate fat when fat spills out of your adipose tissue, the beta cells in your pancreas are also highly susceptible to fat accumulation.

Known as lipotoxicity, the accumulation of excess fat in your beta cells leads to severe beta cell dysfunction (27–38).

In comparison with cells in your liver and muscle, beta cells are particularly sensitive to damage caused by fatty acids because they have a limited ability to protect themselves against damage.

When exposed to high fat concentrations for long periods of time, their antioxidant self-defense mechanisms are inadequate to protect them against dysfunction (33,34).

Step 1: Stressed Beta Cells Make Excess Insulin

The way that beta cells behave depends on a number of factors, including fat concentration, glucose concentration and the amount of time that they are exposed to high levels of either fat or glucose (34). As fat spills over from adipose tissue and the level of whole-body insulin resistance increases over time, your pancreas responds by making more insulin, to overpower your muscle and liver into behaving properly. In effect, your beta cells are saying…

“Wow the amount of glucose in the blood is incredibly high. I better make more insulin so that the liver and muscle will have no choice but to take it up. When the going gets tough, the tough make insulin!”

Because the beta cells are now over producing insulin beyond their physiologically normal level, they enter a state of cellular stress. As this cycle continues and the degree of insulin resistance increases over time, the amount of insulin produced by your pancreas also continues to increase.

Insulin sensitivity insulin resistance

Step 2: Beta Cells Maximize Insulin Production

At a certain point, insulin production no longer increases – your beta cells are sufficiently stressed and their production of insulin is maximized. At this point, your beta cells simply cannot make more insulin. In some individuals, this process can take many years to develop, and in others this process occurs very quickly.

The amount of insulin produced at the peak is highly variable between individuals; some people hit peak insulin production at 150% of normal whereas others hit peak insulin production at 450% of normal. The amount of insulin produced at peak depends on both the number of beta cells and the strength of the beta cells, both of which are variable between individuals. More insulin is capable of being produced as both the size of the beta cell population and the relative strength each individual beta cell increases. Despite these individual differences, the common thread between all insulin resistant individuals is that beta cells stress triggers excess insulin production beyond the physiological normal amount.

Step 3: Stressed Beta Cells Commit Suicide

There comes a point in the life of a stressed beta cell where it is more advantageous to commit suicide than it is to stay alive. At this point, beta cells will undergo a process called apoptosis (programmed cell death). This is a point of no return. When a large population of stressed beta cells commit suicide together, insulin production falls rapidly in a short period of time. As a result of this massive die off, insulin production falls to below normal physiological levels. This state is called type 2 diabetes.

In the same way that peak insulin production varied between individuals, the amount of beta cell suicide is also a highly variable process.

Some individuals retain 60% of their original beta cell mass whereas others will drop to as low as 20% of their original beta cell mass. Autopsies have revealed that in the majority of patients with type 2 diabetes, more than half of the beta cell population has been permanently killed off (22).

In this state, only a small population of beta cells are now responsible for secreting enough insulin to satisfy your entire body. As you may be able to predict, this job is extremely difficult unless you help your muscle and liver significantly reduce their requirement for insulin. Fortunately, these remaining beta cells are strong enough to remain alive, however they are at risk for death as long as insulin resistance persists.

After the age of twenty, your body stops making new beta cells; beta cell death is therefore considered irreversible (39). The question then becomes this: if the level of insulin resistance is significantly reduced, can the remaining beta cell population produce enough insulin to meet the demands of your entire body? In other words, are the remaining “soldiers” strong enough to withstand the test of time?

Fortunately for you, the answer is almost always yes. Even when beta cell mass has been significantly compromised, the remaining beta cell population is often capable of producing sufficient insulin for all tissues. But in order to do this, you must reduce your level of whole-body insulin resistance by reducing your intake of dietary fat, otherwise the remaining beta cells remain stressed and will continue to commit suicide.

Below is a picture to summarize the process of beta cell death:

beta cell death insulin

Step 4: Reverse Insulin Resistance Before It’s Too Late!

A low-fat, plant-based whole foods approach is the most powerful method of reducing whole-body insulin resistance and preserving long-term beta cell function. Period. End of story.

If you’re interested in adopting a low-fat, plant-based whole foods diet for increased energy, weight loss, reduced blood glucose and exceptional long-term health, contact me using the widget below and let’s see if a group-based coaching program is right for you.

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If you have personal experience in reversing insulin resistance in type 1 diabetes, prediabetes or type 2 diabetes, leave a comment below and tell us about your experience. Share your story with the world, it makes a HUGE difference to those thinking about starting.

References

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  1. Boden G. Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver. Curr Diab Rep. 2006 Jun;6(3):177–81.
  2. Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes. 1997 Jan;46(1):3–10.
  3. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β-cell dysfunction. Eur J Clin Invest. 2002 Jun 1;32:14–23.
  4. Boden G. Fatty acid-induced inflammation and insulin resistance in skeletal muscle and liver. Curr Diab Rep. 2006 Jun;6(3):177–81.
  5. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β-cell dysfunction. Eur J Clin Invest. 2002 Jun 1;32:14–23.
  6. Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-Induced Insulin Resistance in Human Muscle Is Associated With Changes in Diacylglycerol, Protein Kinase C, and IκB-α. Diabetes. 2002 Jul 1;51(7):2005–11.
  7. Savage DB, Petersen KF, Shulman GI. Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance. Physiol Rev. 2007 Apr 1;87(2):507–20.
  8. Xiao C, Giacca A, Carpentier A, Lewis GF. Differential effects of monounsaturated, polyunsaturated and saturated fat ingestion on glucose-stimulated insulin secretion, sensitivity and clearance in overweight and obese, non-diabetic humans. Diabetologia. 2006 Apr 5;49(6):1371–9.
  9. Wang P-Y, Kaneko T, Wang Y, Tawata M, Sato A. Impairment of Glucose Tolerance in Normal Adults Following a Lowered Carbohydrate Intake. Tohoku J Exp Med. 1999;189(1):59–70.
  10. Martins AR, Nachbar RT, Gorjao R, Vinolo MA, Festuccia WT, Lambertucci RH, et al. Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function. Lipids Health Dis. 2012;11:30.
  11. Delarue J, Magnan C. Free fatty acids and insulin resistance. Curr Opin Clin Nutr Metab Care. 2007 Mar;10(2):142–8.
  12. Griffin ME, Marcucci MJ, Cline GW, Bell K, Barucci N, Lee D, et al. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes. 1999 Jun;48(6):1270–4.
  13. Yu C, Chen Y, Cline GW, Zhang D, Zong H, Wang Y, et al. Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle. J Biol Chem. 2002 Dec 27;277(52):50230–6.
  14. Hirabara SM, Curi R, Maechler P. Saturated fatty acid-induced insulin resistance is associated with mitochondrial dysfunction in skeletal muscle cells. J Cell Physiol. 2010 Jan;222(1):187–94.
  15. Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest. 2000 Jul;106(2):171–6.
  16. Roden M, Price TB, Perseghin G, Petersen KF, Rothman DL, Cline GW, et al. Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest. 1996 Jun 15;97(12):2859–65.
  17. Silveira LR, Fiamoncini J, Hirabara SM, Procópio J, Cambiaghi TD, Pinheiro CHJ, et al. Updating the effects of fatty acids on skeletal muscle. J Cell Physiol. 2008 Oct;217(1):1–12.
  18. Roden M. How free fatty acids inhibit glucose utilization in human skeletal muscle. News Physiol Sci Int J Physiol Prod Jointly Int Union Physiol Sci Am Physiol Soc. 2004 Jun;19:92–6.
  19. Galgani JE, Moro C, Ravussin E. Metabolic flexibility and insulin resistance. Am J Physiol Endocrinol Metab. 2008 Nov;295(5):E1009-1017.
  20. Yamamoto Noguchi CC, Kunikane N, Hashimoto S, Furutani E. Mixed model of dietary fat effect on postprandial glucose-insulin metabolism from carbohydrates in type 1 diabetes. Conf Proc Annu Int Conf IEEE Eng Med Biol Soc IEEE Eng Med Biol Soc Annu Conf. 2015 Aug;2015:8058–61.
  21. Sumiyoshi M, Sakanaka M, Kimura Y. Chronic Intake of High-Fat and High-Sucrose Diets Differentially Affects Glucose Intolerance in Mice. J Nutr. 2006 Mar 1;136(3):582–7.
  22. Taylor R. Banting Memorial lecture 2012: reversing the twin cycles of type 2 diabetes. Diabet Med J Br Diabet Assoc. 2013 Mar;30(3):267–75.
  23. Pańkowska E, Błazik M, Groele L. Does the fat-protein meal increase postprandial glucose level in type 1 diabetes patients on insulin pump: the conclusion of a randomized study. Diabetes Technol Ther. 2012 Jan;14(1):16–22.
  24. Smart CEM, Evans M, O’Connell SM, McElduff P, Lopez PE, Jones TW, et al. Both dietary protein and fat increase postprandial glucose excursions in children with type 1 diabetes, and the effect is additive. Diabetes Care. 2013 Dec;36(12):3897–902.
  25. Paterson M, Bell KJ, O’Connell SM, Smart CE, Shafat A, King B. The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes: Implications for Intensive Diabetes Management. Curr Diab Rep. 2015 Jul 23;15(9):1–9.
  26. Neu A, Behret F, Braun R, Herrlich S, Liebrich F, Loesch-Binder M, et al. Higher glucose concentrations following protein- and fat-rich meals – the Tuebingen Grill Study: a pilot study in adolescents with type 1 diabetes. Pediatr Diabetes. 2015 Dec 1;16(8):587–91.
  27. Haber EP, Ximenes HMA, Procópio J, Carvalho CRO, Curi R, Carpinelli AR. Pleiotropic effects of fatty acids on pancreatic beta-cells. J Cell Physiol. 2003 Jan;194(1):1–12.
  28. Haber EP, Procópio J, Carvalho CRO, Carpinelli AR, Newsholme P, Curi R. New insights into fatty acid modulation of pancreatic beta-cell function. Int Rev Cytol. 2006;248:1–41.
  29. Kraegen EW, Cooney GJ, Ye JM, Thompson AL, Furler SM. The role of lipids in the pathogenesis of muscle insulin resistance and beta cell failure in type II diabetes and obesity. Exp Clin Endocrinol Diabetes Off J Ger Soc Endocrinol Ger Diabetes Assoc. 2001;109 Suppl 2:S189-201.
  30. Kusminski CM, Shetty S, Orci L, Unger RH, Scherer PE. Diabetes and apoptosis: lipotoxicity. Apoptosis Int J Program Cell Death. 2009 Dec;14(12):1484–95.
  31. Manco M, Calvani M, Mingrone G. Effects of dietary fatty acids on insulin sensitivity and secretion. Diabetes Obes Metab. 2004 Nov;6(6):402–13.
  32. Poitout V, Robertson RP. Minireview: Secondary beta-cell failure in type 2 diabetes--a convergence of glucotoxicity and lipotoxicity. Endocrinology. 2002 Feb;143(2):339–42.
  33. Robertson RP, Harmon J, Tran POT, Poitout V. β-Cell Glucose Toxicity, Lipotoxicity, and Chronic Oxidative Stress in Type 2 Diabetes. Diabetes. 2004 Feb 1;53(suppl 1):S119–24.
  34. Sharma RB, Alonso LC. Lipotoxicity in the pancreatic beta cell: not just survival and function, but proliferation as well? Curr Diab Rep. 2014 Jun;14(6):492.
  35. Shimabukuro M, Zhou YT, Levi M, Unger RH. Fatty acid-induced beta cell apoptosis: a link between obesity and diabetes. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2498–502.
  36. Unger RH, Grundy S. Hyperglycaemia as an inducer as well as a consequence of impaired islet cell function and insulin resistance: implications for the management of diabetes. Diabetologia. 1985 Mar;28(3):119–21.
  37. Unger RH, Zhou YT. Lipotoxicity of beta-cells in obesity and in other causes of fatty acid spillover. Diabetes. 2001 Feb;50 Suppl 1:S118-121.
  38. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes. 1995 Aug;44(8):863–70.
  39. Cnop M, Hughes SJ, Igoillo-Esteve M, Hoppa MB, Sayyed F, van de Laar L, et al. The long lifespan and low turnover of human islet beta cells estimated by mathematical modelling of lipofuscin accumulation. Diabetologia. 2010 Feb;53(2):321–30.
About The Author

Cyrus Khambatta

Diagnosed with type 1 diabetes at the age of 22, I have spent over a decade learning the fundamentals of nutrition at the doctorate level. My goal is to share my knowledge of practical nutrition and fitness with people with prediabetes, type 1 and type 2 diabetes. Diabetes is an OPPORTUNITY to attain excellent health. Reversing the effects of insulin resistance can be a fun and enjoyable process if the right system is in place. That's why I've spent over 10 years developing a rock solid system that can minimize blood glucose variability and insulin resistance.

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