By Juliana Xie. Pan-creas! Greek: “pan” = all; “creas” = flesh Pancreas is like a fish!...
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Transcript of By Juliana Xie. Pan-creas! Greek: “pan” = all; “creas” = flesh Pancreas is like a fish!...
PANCREAS AND GLUCOSE
By Juliana Xie
Pan-creas!•Greek: “pan” = all; “creas” = flesh
•Pancreas is like a fish! Head, body, and tail.
• Important anatomical relationships
Why care about the pancreas?• The diseased pancreas can cause a LOT of trouble
• Diabetes: • In the United States, 25.8 million adults and children (8.3% of population) have diabetes
• Systemic disease
•Pancreatic cancer – 4th most common cause of cancer-related death, extremely poor prognosis
• Pancreatitis is an emergency situation
What makes the pancreas such an important organ?•Outline pancreatic gross and cellular anatomy
•Discuss the normal function of the pancreas in glucose metabolism
Pancreas: two major roles
•Control the sugar levels in the body
•Produce enzymes that CHOP (digest) food1) Exocrine
2) Endocrine
A closer look: Endocrine Pancreatic cells Islets of Langerhans
has FOUR major cell types:
1) Alpha cell
2) Beta cell
3) Gamma cell (PP cell)
4) Delta cell
Islets of Langerhans!!!
A closer look: Endocrine Pancreatic cells1) Alpha cells glucagon2) Beta cells insulin3) Gamma cells pancreatic polypeptide4) Delta cells somatostatin
• Observe how these cells lie in close proximity of capillaries.
Alpha cells• Alpha cells make up 33-46% of the human islet cells
• Make and secrete glucagon to elevate glucose levels in bloodClinical correlation:Too much glucagon – glucagonoma-rare tumor of the alpha cells that cause up to 1000-fold overproduction of glucagon-blood glucose raises via gluconeogenesis and lipolysis-causes diabetes mellitus
Beta cells• Make up 65-80% of the cells in the islets
•Pathology:•Type 1 diabetes mellitus
• Insulin-dependent diabetes•Autoimmune disease• Body cannot make insulin
• Type 2 diabetes mellitus•Non insulin-dependent diabetes• Body can still make insulin, but tissues are insensitive to its actions
Gamma cells• Predominantly reside in the head of the pancreas
•Makes and releases pancreatic polypeptide (PP) in response to ingestion of food
• Inhibitory functions• Found to be elevated in anorexia nervosaClinical correlation:-too much PP – Pancreatic polypeptidoma-can cause weight loss, diabetes mellitus
Delta Cells• Produce somatostatin INHIBITORY• Produced in multiple tissues, antigrowth effects
• Suppress the release of insulin and glucagon Clinical correlation:Too much somatostatin – somatostatinoma-extreme reduction in secretion of insulin and cause diabetes.
Pancreas and Glucose Homeostasis• Glucose regulation works in a system of organs
Pancreas and Glucose Homeostasis
Clinical correlation: glucose test• Normal fasting blood sugar: 72 to 126 mg/dL
• After a meal: less than 180 mg/dL 90 minutes after eating is normal
Hormonal Regulation of Glucose Metabolism
LUKE D. PIPER
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the body responds
Goals of Glucose Regulation
• Get glucose into cells for utilization/storage Glucose is primary fuel for cellular energy
Can be stored in liver and muscles as glycogen
• Breakdown stored energy into glucose Glycogen breakdown can quickly supply glucose
Lipids and proteins can be converted to glucose
• Keep blood glucose from becoming too low or too high
Hypo- and hyperglycemia can both be dangerous
Insulin
Glucagon
Both
Insulin
• Polypeptide hormone
• Produced in the Pancreas Specifically, the β cells of the islets of Langerhans
• Principle action: facilitates glucose uptake and glycogen synthesis
• Other actions: facilitates lipid and protein synthesis
• Insulin is primarily anabolic
Insulin is stored as a hexamer (left).
Its active form is a monomer (below).
Insulin: Principle Actions
• Glucose uptake Signaling pathway increases membrane expression of GLUT4 transporter
Allows glucose to enter cell
Especially important in muscle and adipose
• Muscles: energy and storage
• Adipose: long-term storage
Note: not all cells need insulin to get glucose
• Glycogen synthesis Signaling pathway promotes storage of glucose as glycogen
Especially important in liver
Insulin Action: Visual Aid
Recall: insulin is anabolic
Insulin Regulation
• Insulin secretion is stimulated by: High blood glucose levels
Amino acid ingestion
Gastrointestinal hormones (e.g., cholecystokinin)
• Insulin secretion is inhibited by: Scarcity of dietary fuel
Epinephrine
Glucagon
• Also a polypeptide hormone
• Also produced in the pancreas Specifically, the α cells of the islets of Langerhans
• Principle action: mobilization of stored energy
• Directly opposes most of insulin’s effects Pancreas coordinates release of glucagon and insulin
• Glucagon is primarily catabolic
…yep, this is it.
Glucagon: Principle Actions
• Increases blood glucose Triggers glycogen breakdown in liver (glycogenolysis)
Activates glucose production pathways (gluconeogenesis)
• Elicits breakdown of stored lipids (lipolysis) Glycerol used in gluconeogenesis
Free fatty acids can be made into ketone bodies
• Amino acid metabolism Taken up by liver; used in gluconeogenesis
• Theme: glucagon engages energy reserves
Glucagon Action: Visual Aid
Glucagon operates via G-protein signalingto activate protein kinase A. Here, PKA activates enzymes involved in glycogenbreakdown and deactivates enzymes involved in glycogen synthesis.
In adipose, the same type of pathway is used. There, the pathway targets enzymes involved in lipolysis.
Glucagon Regulation
• Glucagon secretion is stimulated by: Low blood glucose
Amino acid ingestion
Epinephrine
• Glucagon secretion is inhibited by: High blood glucose
Insulin
Super Fun and Totally Cool Mnemonic
• Insulin gets glucose into cells (so that they can use it or store it)
• Glucagon is for when the glucose is gone (and you need to mobilize storage)
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the body responds
Fact
• Blood glucose must be tightly regulated
• Normally, insulin and glucagon work together to ensure it is
• Problems arise when this regulation fails
Hyperglycemia
• Too much glucose in blood Often suggests malfunction in insulin pathway
• Often seen in diabetes mellitus
• Chronic hyperglycemia carries several long term effects: Increased risk of cardiovascular disease and stroke
Frequent hunger, thirst, and need for urination
Tissue damage (e.g., retinopathy, nephropathy, neuropathy)
Ketoacidosis
(Sneak preview for your 11/11 lecture)
Hypoglycemia
• Too little glucose in blood
• A number of potential causes:
Improper insulin dosage in diabetes patients
Oversecretion of bodily insulin
Long-term fasting
Liver dysfunction due to alcohol
• Body responds via glucagon and epinephrine
• This is a medical emergency CNS requires continuous supply of glucose
Even brief denial of glucose to brain can cause long-term damage
The Brain.Most researchers agree: it is important.
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the body responds
Feeding, Fasting, and Blood Sugar
• Feeding: Consuming a meal Breakdown of carbs = sharp increase in blood glucose
Body responds with insulin
Glucagon inhibited (unless meal is predominantly protein)
• Fasting: Skipping a meal, or otherwise refraining from eating Glucose steadily falling
Insulin falls, glucagon/epinephrine rise
Body calls upon storage to meet energy demands
Fun fact: typical 70kg man has about 135,000 calories stored as fat
Feed/Fast Cycle Summarized
The key is that insulin and glucagonwork in tandem to maintain blood glucose levels in response to foodintake, or lack thereof.
Overview: Learning Objectives
Assuming I know what I’m doing up here, students should ultimately be able to:
• Discuss the actions of insulin and glucagon
• Discuss the mechanisms that regulate secretion of insulin and glucagon
• Discuss potential problems arising from poor glucose regulation
• Discuss how eating and fasting affect blood sugar, and how the body responds
My Personal Takeaway
• The human body is elegantly designed to control many physiological parameters essential for its survival.
• At the very least, I hope you take away some appreciation for the incredible capabilities of our physiology.
• Regardless, thank you for your attention and have a good week.
“Well that sure was fun. But hey everyone, make sure you come onback on November 11th for a fascinating presentation on diabetes.”
-Wilford Brimley