Physiology 2130 Lecture Notes - Lecture 58: Diabetes Mellitus Type 1, Polyphagia, Insulin Resistance
1 May 2018
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Lecture 058: Diabetes and insulin resistance
Diabetes Mellitus
● “Sweet urine disease” (large volume)
● Characterized by
○ Hyperglycemia
■ High blood sugar
○ Polyphagia
■ Eating with weight loss
○ Polyuria
■ High urine volume
○ Glycosuria
■ Glucose in urine
○ Water and electrolyte loss
● In severe cases:
○ Ketosis (high ketones
○ Acidosis
○ Coma and death
● Long term complications
○ Retinopathy
○ Nephropathy
○ Angiopathy
○ Increase susceptibility to infection
Type I Diabetes
● Insulin dependent
○ A failure to secrete sufficient insulin to regulate glucose utilization
● Autoimmune destruction of the pancreatic -cells
○ T-cells from the thymus destroy the islet -cells
● Early onset (“juvenile diabetes”)
● 10% of diabetics
● Early symptoms
○ High glucose in urine and blood
○ Dehydration
○ Low energy
Type II Diabetes
● Insulin resistant and impaired insulin secretion
○ Have insulin but not responding to it
● Associated with “lifestyle” issues
○ Overweight
○ Sedentary
● Onset is midlife
○ Occuring in a younger population due to childhood obesity
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● 90% of diabetics
What happens without Insulin?
● Inability to transport glucose into muscle and adipose cells
○ Need an alternate energy source needed
■ Breakdown protein and fat instead
○ Increased gluconeogenesis by using amino acids
■ Muscle is broken down into amino acids, converted into glucose in liver
● Glucose is used by the brain and liver
● Results in:
○ Muscle wasting
○ Weight loss
○ Increased lipolysis
■ Mobilization of triglycerides and free fatty acids from stores
■ Free fatty acid can be used in the TCA cycle to generate ATP
● Free fatty acid oxidation
■ However, this process leads to ketone byproducts
● High ketones are a marker of diabetes
● Leads to ketoacidosis
○ Cell death (toxic)
● Fate of high serum glucose
○ Increased glucose filtration in the kidneys
■ Leads to increased water excretion (by diffusion) and dehydration
■ Stress the kidney
○ Glucose is converted into sorbitol (via the polyol pathway)
■ Sorbitol is damaging to the lens, nerves and capillaries
○ Increased glycosylation of proteins
■ Adding cellulose via the glyoxal pathway
■ Glycosylation impairs protein function and leads to protein misfolding
○ De novo synthesis of diacylglycerol (DAG)
■ High levels of DAG in the kidney cells increases PKC activation
● Leads to nephropathy
What is insulin resistance?
● Decreased cellular response to insulin
○ Lots of insulin but the receptor is not
responding
● Associated with hyperglycemia and impaired
insulin secretion (not full function capacity)
● Risks
○ Diet, lifestyle, genes (indirect)
○ Obesity
Mechanism of Insulin Resistance
● Changes in insulin receptors phosphorylation
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
A failure to secrete sufficient insulin to regulate glucose utilization. T-cells from the thymus destroy the islet (cid:533)-cells. Have insulin but not responding to it. Occuring in a younger population due to childhood obesity. Inability to transport glucose into muscle and adipose cells. Muscle is broken down into amino acids, converted into glucose in liver. Glucose is used by the brain and liver. Mobilization of triglycerides and free fatty acids from stores. Free fatty acid can be used in the tca cycle to generate atp. However, this process leads to ketone byproducts. High ketones are a marker of diabetes. Leads to increased water excretion (by diffusion) and dehydration. Glucose is converted into sorbitol (via the polyol pathway) Sorbitol is damaging to the lens, nerves and capillaries. Glycosylation impairs protein function and leads to protein misfolding. High levels of dag in the kidney cells increases pkc activation. Lots of insulin but the receptor is not responding.
