7 - Endocrine Pancreas (Glucagon)

What cell types secrete glucagon and when does this occur?

alpha cells, when glucose availability falls

Where does glucagon primarily act?

liver

What is the basic function of glucagon?

catabolic hormone mobilizing stored fuel into the blood stream by:

• increases hepatic glycogen breakdown and gluconeogenesis

• contributes to ketone production

What are the stimulators of glucagon?

• hypoglycemia (primary)

• amino acids after protein meal

• exercise and stress

• sympathetic input

• fasting

What are the inhibitors of glucagon?

• hyperglycemia

• insulin within the islet

• somatostatin

• free fatty acids and ketones

What is the effect of somatostatin on the pancreas hormones?

suppresses both insulin and glucagon

What is the effect of amylin on the pancreas hormones?

co-secreted with insulin, helping to limit post-meal glucose rise

What is the effect of pancreatic polypeptide on the pancreas hormones?

product of F-cell with uncertain physiologic significance

What hormone predominates the fed state?

insulin

In fed state, glucose uptake and storage is ___________ (increased/decreased).

increased

In the fed state, glycogen, fat, and protein synthesis ___________ (increase/decrease)

increase

In the fasting state, insulin _______ (rises/falls).

falls

In fasting state, glucagon _______ (rises/falls).

rises

Hepatic glucose production ________ (increases/decreases) during fasting state.

increases

During which state are stored fuels mobilized?

fasting state

What is the result of insulin deficiency or inefficiency?

body cannot fully enter the normal fed state (T1D)

• impairing glucose uptake

• hepatic glucose output remains high

• lipolysis increases

• protein breakdown increases

What is the normal fasting range of glucose?

70-100 mg/dL

What is the result of plasma glucose <70 mg/dL?

hypoglycemia - immediate organ threat, especially the brain

What is the result of acute hyperglycemia?

chronic tissue injury and/or acute metabolic crisis

• glucose in urine is osmotically active

• polyuria

• dehydration

• weight loss

• electrolyte depletion

Why may long-term diabetics be unaware of hypoglycemia?

autonomic warning symptoms may be blunted, cognitive impairment arrives without warning

What is the result of chronic hyperglycemia?

nonenzymatic glycation of proteins contributing to vascular and tissue damage

• major targets are eyes, kidneys, nerves, & blood vessels

Define diabetes mellitus?

a disorder of glucose homeostasis marked by chronic hyperglycemia due to inadequat insulin effect

What is the primary problem of Type 1 diabetes?

insulin deficiency caused by the destruction of pancreatic beta cells

• insulin replacement is required

What is the primary problem of Type 2 diabetes?

insulin resistance often associated with obesity

What are the effects of both types of diabetes?

polyuria, polydipsia, and weight loss when poorly controlled

Define diabetic ketoacidosis

severe insulin deficiency (T1D):

• hyperglycemia due to impaired glucose uptake and increased hepatic glucose output

• lipolysis increases and more ketones are produced, contributing to metabolic acidosis

• causes glycosuria and osmotic diuresis, leading to dehydration

• potassium shifts out of cells when insulin is absent

Define hyperosmolar hyperglycemic state.

hyperglycemia becomes very sever (T2D):

• osmotic diuresis → dehydration

• neurologic symptoms can be prominent