[101] Insulin Resistance

A science-ish explanation of 'insulin resistance' and its effect on specific organs

Source: Ben Bikman, PhD: 'Flipping the Switch: From Insulin Resistance to Type 2 Diabetes'

Intro: Insulin Resistance as a Precursor to Diabetes

  • Healthy biology

    • We consume food (the insulin effect is highest when consuming carbohydrates, and to a lesser extent, protein)

    • Food is broken down to component molecules, of which there is sugar (glucose)

    • Insulin is secreted to shuttle glucose molecules from the bloodstream into organs where it can be used as fuel or stored

  • Insulin resistance (left side of image):

    • When we keep consuming foods that spike insulin levels constantly, our cells (i.e. muscle, liver, pancreas) start becoming resistant to insulin

      • Analogy: the boy who cried wolf

    • Because the cells are resisting (aka. not listening to) insulin's commands, they start to slack off on their jobs of locking up glucose in their respective organs (so it can be used for fuel right now or tomorrow), instead of just letting glucose circulate freely in the bloodstream

    • The insulin-glucose relationship becomes uncoupled, such that more and more insulin is needed to keep blood glucose levels at bay

    • Hyperglycemia: the state where there is too much (hyper) glucose in the bloodstream (glycemia)

  • Diabetes (right side of image): as insulin resistance becomes exacerbated, it hits a point where the body stops responding to it altogether; no amount of insulin can control glucose levels

Stage 1: Insulin Resistance in Muscle Tissue

  • Healthy / normal biology:

    • Remember insulin shuttles glucose from the bloodstream into organs

    • Muscle tissue receives the majority (~70%) of this glucose load

  • Insulin resistance: because of insulin resistance, the delivery of glucose to muscle cells is reduced by half, which means that the remaining 50% still circulates in the bloodstream (leading to hyperglycemia)

Stage 2: Insulin Resistance in the Liver

Normal Liver

Insulin-resistant Liver

  • Healthy / normal biology: insulin regulates two functions in the liver

    • Lipogenesis: production of fat

    • Glycogenesis: production of glycogen (a storage form of glucose)

  • Insulin resistance:

    • Lipogenesis is still activated (so the liver continues to make fat)

    • But glycogenesis is impaired, so the liver isn’t holding on to glucose, which means that the glucose stays circulating in the bloodstream (leading to hyperglycemia)

Stage 3: Insulin Resistance in the Pancreas

Normal Pancreas

Insulin-resistant Pancreas

  • Healthy / normal biology: pancreas has yin-and-yang balance of alpha and beta cells that maintain the homeostasis of steady blood glucose levels

    • Alpha cells: glucagon stimulates them to increase blood glucose

    • Beta cells: insulin stimulates them to decrease blood glucose

    • Under normal circumstances, insulin is dominant over glucagon, which leads to reducing blood glucose levels in healthy bodies

  • Insulin resistance:

    • Alpha cells become insulin resistant, which means they don’t listen to insulin’s orders to reduce blood glucose (leading to hyperglycemia)

Summary: From Insulin Resistance to Type-2 Diabetes

Insulin Resistance to Type-2 Diabetes Paradigm

  • Type-2 diabetes is built on a foundation of insulin resistance

  • First to fall is the adipose tissue: fat cells growing through hypertrophy become insulin resistant and start leaking fats (in the form of ceramides) into other organs of the body

  • Ceramides start spreading in other organs (muscle, liver, pancreas), making them insulin resistant, which leads to higher levels of blood glucose, ultimately leading to diabetes

Disclaimer: I do not own the rights to the materials. All images herein are from Ben Bikman, PhD: 'Flipping the Switch: From Insulin Resistance to Type 2 Diabetes'

Ben Bikman, PhD. Bio

Dr. Benjamin Bikman earned his Ph.D. in Bioenergetics and was a postdoctoral fellow with the Duke-National University of Singapore in metabolic disorders. He is currently a professor of pathophysiology and a biomedical scientist at Brigham Young University in Utah. Dr. Bikman's professional focus as a scientist and professor is to better understand chronic modern-day diseases, with a special emphasis on the origins and consequences of obesity and diabetes, with an increasing scrutiny of the pathogenicity of insulin and insulin resistance. He frequently publishes his research in peer-reviewed journals and presents at international science meetings. Dr. Bikman has long been an advocate of a ketogenic diet in light of the considerable evidence supporting its use as a therapy for reversing insulin resistance. His website InsulinIQ.com promotes dietary clarity, healing, and freedom through evidence-based science about insulin resistance. Employing cell-autonomous to whole-body systems, Dr. Bikman's recent efforts have focused on exploring the intimate associations between the metabolic and immune systems.