Lecture 10: the Pancreas and Liver

Glycolysis

the break down of glucose

Lipolysis

breakdown of fat

Lipogenesis

Fat storage (results in a decrease in glucose)

Glycogenolysis

Breakdown of glycogen stores (inc blood glucose)

Glycogenesis

formation of glycogen from glucose; glucose storage (dec blood glucose)

Gluconeogenesis

Formation of glucose from non carbohydrate substrates

Pancreatic Islets have _______ function

Pancreatic Acini have _______ function

endocrine; exocrine

Insulin and glucagon are the major endocrine hormones that sevr the regulates the body’s metabolism of what

carbohydrates, lipids, and proteins

the ______ gland produces hormones

endocrine

the _______ gland produces digestive enzymes

Exocrine

The ________ are responsible for the secretion of glucagon and insulin

Islets of Langerhans

What do alpha cells synthesize and secrete

Glucagon

What do beta cells synthesize and secrete

Insulin and amylin

What do Delta cells synthesize

somatostatin and gastrin

What do PP cells synthesize

pancreatic polypeptides

What do D1 cells secrete

vasoactive intestinal peptide

What do enterochromaffin cells secrete

serotonin

The release of insulin in triggered by

hyperglycemia, inc in blood amino acids, and GLP-1

In regards to insulin release:
Parasympathetics activity ______

sympathetic activity ______

amplifies, inhibits

What are the primary target cells/tissues for insulin

Liver, muscle, adipose tissue

Insulin target receptors are receptors with what kind of activity

tyrosine kinase

What is the action caused by the secretion of insulin (whole body/tissue)

dec in plasma glucose via increased transport into cells, and increase in the metabolic use of glucose

What is the action caused by the secretion of insulin (cellular level)

Increases glycogen synthesis, increases aerobic metabolism of glucose, increases protien and triglyceride synthesis

The release of glucagon is triggered by

hypoglycemia and inc in blood amino acids

What is the target cells/tissues for glucagon

liver

What is the target receptor/2nd messenger for glucagon

G protein coupled receptor linked to cAMP

What is the action caused by the secretion of glucagon (whole body/tissue)

inc plasma glucose by glycogenolysis and gluconeogenesis; increases lypolysis leading to ketogenesis in the liver

In the fed state ______ dominates

in the fasted state ______ dominates

Insulin; Glucagon

What are some processes that are occurring while in the fed/ insulin dominated state

inc glucose oxidation, inc glycogen synthesis, inc fat synthesis, inc protein synthesis

What are some processes that are occurring while in the fasted/ glucadon dominated state

inc glycogenolysis, inc gluconeogenesis, inc ketogenesis

insulin promotes ________ processes

Glycogen promotes _______ processes

anabolic, catabolic

______ of insulin receptors is a key component to maintaining normal cellular function

sensitivity

_________ facilitates glucose diffiction

GLUT 4 (glucose transporter type 4)

______ is dependent on insulin

______ is independent of insulin

GLUT 4, GLUT 2

Explain the process of how Beta cells sense glucose and release insulin

glucose into the cell via GLUT2, increasing glucose increases ATP triggering K+ channels to close, cell depolarization, Ca2+ influx and exocytosis of stored insulin

Glucose stimulation occurs in a _______ spike

biphasic

Explain the glucose biphasic spike

3-5 minutes after stimulation insulin rapidly and significantly increases from stored insulin, over the next 12-20 minutes a second peak occurs more gradually

Insulin directly enhances what processes

Glycogen synthesis and glycolysis

Insulin stimulates the glycolytic use of glucose by increasing the activity of several enzymes in the glycolytic pathway that perform what important step

conversion of glucose to pyruvate

Insulin inhibits what processes

glycogen breakdown and gluconeogenesis

How does insulin inhibit the breakdown of glycogen

inhibits glycogen phosphorylase (enzyme that degrades glycogen)

How does insulin inhibit gluconeogenesis

decreasing key substrate, free fatty acids

Insulin increases lipogenesis in what two areas

liver, adipose cells

Insulin stimulates _______ into adipose cells

lipid uptake

Glucagon secretion in triggered by what

low plasma glucose (chief), Norepinephrine, and epinephrine

Glucagon increases glucose levels via stimulation of

glycogenolysis and gluconeogenesis

Glucagon increases the avaliability of fatty acids via the activate of what in adipose cells

hormone sensitive lipase

Glugacon decreases plasma amino acid levels via increased uptake into the live cells, these cells are funnelied into gluconeogenesis to do what

provide carbon backbone

under the influence of glucagon the activation of hormone sensitive lipase increases the breakdown of what

adipose tissue triglyceride stores into FFAs

FFAs and amino acids are oxidized in the lived to acetyl CoA unfer the influyence of glucagon. What does the buildup of acetyl CoA drive the formation of

Keytones

somatostatin is produced in what cells of the pancreas

Delta cells

pancreatic polypeptide is synthesized in the PP cells and secreted in reporse to protein containing meals, what does this stimulate

secretion of gastric and intestinal enzymes; inhibits intestinal motility

_____ is co-secreted with insulin by beta cells

Amylin

Amylin regulates blood glucose levels by

delaying gastric emptying (satiety) and suppressing glucagon secretion after meals (antihyperglycemic effect)

What are the two Incretins

Glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP)

what are the ways that Incretins control postprandial glucose levels

promote glucose-dependent insulin secretion, inhibit glucagon synthesis, promote hepatic glucose secretion, and delay gastric emptying

Hypothalamic somatostatin inhibits

Growth hormone and TSH

growth hormone is a metabolic hormone that is pulsatile, peaking at night, and primarily affects the grow of

skeletal muscles and long bones

70% of GH release occurs when

during sleep

GH peaks when and decreases with what

during adolescence and decreases with age

what conditions cause an increased release of GH

dec glucose, dec FFA, fasting, exercise, stress, a1 agonist

what conditions cause a decreased release of GH

inc glucose, inc FFA, obesity, aging, somatomedins (IGFs), somatostatin, B-agonist

What are some direct actions of GH

Inc lipolysis, inc protein synthesis, and dec insulin sensitivity

what are some indirect actions of GH that are mediated by IGF-1

promotes skeletal growth, protein synthesis, and cell proliferation

Disorder of IGF-1 that causes excessive growth of the hands, feet, jaw, and internal organs in adulthood

Acromegaly

Abnormally high linear growth due to the excessive action of IGF-1 before the close of the growth plates during childhood

What is a common finding among a large percentage of patients with acromegaly

pituitary tumor (somatotroph adenoma of the pituitary)

what are some potential consequences of excess GH

dec life span, cardiomyopathy, respiratory disease, arthropathy, neuropathy, diabetes, metabolic syndrome, inc risk of malignancies

what are some potential consequences of GH deficit

hypoglycemia, impaired bone growth, protein catabolism, in TG, Inc LDL/dec HDl, low energy, decrease interest in hobbies/ social interaction

Which type of diabetes is due to autoimmune destruction of b-cells

Type 1

Which type of diabetes is due to progressive loss of b-cell insulin secretion

Type 2

What are labs run to test for diabetes

hemoglobin A1c, random blood glucose, glucose tolerance test

what does a persons A1c have to be to be considered diabetic

greater than or equal to 6.5

what are some common signs any symptoms of a patient with diabetes

polyuria, polydipsia, weight loss, blurry vision, hypotension, and paresthesias

diabetes type 1 is the results of self-reactive ______ destruction of Beta cells

T-cell

What is the major mechanism of diabetes type 2

insulin resistance and decreased insulin secretion by beta cells

metabolic syndrome is one risk factor for diabetes, what is it

central obesity, dyslipidemia, prehypertension, and elevated fasting blood glucose levels

How is is glucagon impacted in type 2 diabetes

pancreatic alpha cells are less responsive to glucose inhibition

Amylin is decreased in type ____ diabetes

Ghrelin is decreased in type ____ diabetes

1 and 2; only type 1