Lect 29 - homeostasis of plasma glucose, diabetes mellitus

Flashcards reviewing key concepts related to glucose homeostasis, insulin, glucagon, and diabetes mellitus based on lecture notes.

Why is blood glucose concentration so important for brain cells?

Brain cells are largely dependent on glucose as an energy source.

What is the function of alpha cells in the pancreatic islets?

Secrete glucagon which increases blood glucose levels.

What is the function of beta cells in the pancreatic islets?

Secrete insulin which reduces blood glucose levels.

How does insulin correct hyperglycemia?

Facilitates glucose uptake into cells of most body tissues, correcting hyperglycemia.

insulin signal transduction pathway

1. insulin binds to alpha subunits of insulin receptor on cell surface

2. causes beta subunits to become activated through autophorylation

3. activaed beta subunits phosphorylate intracellular proteins —> insulin response substrates (IRS)

4. trigger multiple effects

• insertion of GLUT4 transporters into cell membrane of muscle and fat cells

• activation or inactivation of specific enzyme pathways

5. GLUT4 transporter lets glucose enter cell

• glucose transport

• protein synthesis

• fat synthesis

• glycogen synthesis

What nutrient uptake and storage processes does insulin promote?

• Glucose to glycogen (muscle and liver),

• glucose to fatty acids and triglycerides (adipose and liver),

• amino acids to protein (muscle and other cells).

What processes occur in the body when there is no insulin (simulating starvation)?

• Mobilizes glycogen stores,

• breaks down protein,

• mobilizes fat stores,

• increases ketone production.

What are the effects of insulin on skeletal muscle?

• Increase glucose entry into muscle cells via GLUT4 (insulin dependent)

• Increased glycogen synthesis in muscles

• Increased transport of amino acids into muscle (and other cells)

• Increased protein synthesis

• Inhibition of protein breakdown

What are the effects of insulin on adipose tissue?

• Increase glucose transport into adipose cells via GLUT4 (facilitated diffusion)

  • Specific molecule such as glucose binds to receptor site on the integral membrane protein transporter

  • Shape of the protein then changes, moving the molecule across the plasma membrane

• Increased synthesis and storage of triacylglycerols

• Insulin inhibits lipolysis (TAGs to fatty acids)

What are the effects of insulin on the liver?

• uptake of glucose and conversion to glycogen

  • entry into hepatocytes mainly via GLUT2 (insulin independent)

• fatty acid synthesis

  • insulin promotes conversion of excess glucose into fatty acids

  • fatty acids packaged into very low density lipoprotein (VLDL) enter blood and transported to other tissues

• inhibits glycogenolysis

  • glycogen —> glucose

• inhibits gluconeogenesis

  • production of new glucose from non-carbohydrate sources

• suppresses formation of ketone bodies

When is glucagon secreted?

Primarily in response to hypoglycemia (low blood glucose).

What are the 4 effects of glucagon on the liver?

• Breakdown of glycogen to glucose (glycogenolysis)

• production of 'new' glucose by hepatocytes (gluconeogenesis)

• prmote release of glucose from liver cells into blood

• promote breakdown of triglycerides and release of fatty acids from adipose

What are the historical symptoms of diabetes mellitus?

• Passing large volumes of urine (polyuria),

• excessive drinking/thirst (polydipsia),

• excessive hunger (polyphagia).

What is the primary characteristic of Type I diabetes?

Essentially no insulin production by beta cells due to autoimmune destruction of beta cells

What are some acute symptoms of Type 1 Diabetes?

• Passing urine frequently (polyuria),

• excessive thirst (polydipsia),

• excessive hunger (polyphagia),

• tiredness,

• weight loss

What is the primary treatment for Type I diabetes and what risk does it pose?

Insulin, which poses the risk of hypoglycemia.

What is the primary characteristic of Type II diabetes?

Reduced sensitivity to the effects of insulin (hyposensitivity).

What are some causes of Type II diabetes?

Inactivity, poor diet, and obesity.

What are some treatments for Type II diabetes?

• Weight reduction,

• Metformin,

• SGLT2 inhibitors (loose glucose in urine)

• GLP-1 receptor agonists, Sulphonylurea drugs, (increase insulin secretion)

• Acarbose. (slow down absorption of glucose from intestines)

What are key characteristics of Type 1 diabetes?

Always requires insulin; can result in pathology related to chronic hyperglycemia.

What are key characteristics of Type 2 diabetes?

May end up requiring insulin to maintain BGL control; can result in pathology related to chronic hyperglycemia.

What are some pathological effects of chronic hyperglycemia?

• Diabetic retinopathy,

• diabetic nephropathy,

• atherosclerosis,

• diabetic neuropathy.

location of pancreas and features?

• located in duodenum, consists of head, body, and tail

• 99% of pancreatic cells are clustered into acini that secrete eznymes into ducts that empty into intestine

• small clusters of endocrine cells amongst acini (pancreatic islets or Islets of Langerhans)

Insulin features?

• protein hormone synthesised on rER of beta cells

  • preprohormone with A, B, & C chains

  • C chain removed in golgi apparatus

• insulin and C peptide are released from beta cells with increased BGL

• circulate unbound in plasma for aroun 10-15 minutes

what happens when glucose and insulin levels are low in skeletal muscles?

muscle uses fatty acids for energy

features of glucagon?

• polypeptide hormone secreted by alpha cells of pancreatic islets

• exerts affects mainly on liver

What are some chronic symptoms of Type 1 Diabetes?

• poor healing

• infection risk

• cardiovascular disease

• renal disease

• diabetic retinopathy

• diabetic neuropathy

type 1 diabetes symptoms related to activation of the SNS

• tachychardia

• palpitations

• diaphoresis

• tremor

• pallor

• anxiety

type 1 diabetes symptoms due to inadequate blood glucose for normal brain function

• Headache

• Dizziness

• Irritability

• Fatigue

• Confusion

• Visual changes

• Hunger

continuous glucose monitors (CGMs)

subcutaneous BGL sensor

can be coupled with insulin pump

for diabetes type 1

what is hyposecretion?

when diabetes type 2 has progressed, beta cells may get worn out and secrete less insulin —> worsens BG control