Glucose Regulation What is diabetes? Cells need sugar—ATP and the Krebs Cycle What comes in through the gut—basic nutrition Role of liver in processing nutrients, storing glucose Absorptive Pathways and role of insulin from pancreas Post-absorptive Pathways Understanding Diabetes

Diabetes mellitus—”starvation amidst plenty” Type I Juvenile onset Pancreas beta cells die, no insulin produced Type II Adult onset Complicated set of factors, some insulin production Goal—understand why we need insulin

Cells and Glucose All cells of body need constant glucose supply, especially nervous tissue Most other nutrients can be converted into glucose or derivatives for making ATP ATP is celluar “gasoline”

Glycolysis and Kreb’s Cycle Main way that cells make ATP Glucose is principle reactant

Why not eat just sugar?

Essential Amino Acids Only additional nutrients that body can’t produce Needed for making proteins Also some vitamins and minerals must come from diet

What happens to the rest of what we eat?

Interconversion of Nutrients Almost everything we eat can be converted and used by Kreb’s cycle

We need some other nutrients— essential amino acids, vitamins, minerals Our body also uses fats and proteins directly from diet Why not eat just sugar?

What keeps sugar constantly available in blood? Immediately after a meal, nutrients are flowing into blood across wall of stomach, small intestines Between meals, when food has mostly been digested, nutrients are not available Nonetheless, blood sugar levels are kept virtually constant How is this possible? Role of liver in temporary storage of glucose as glycogen Differences in “absorptive” and “post-absorptive” metabolic pathways

Liver STRUCTURE Large ventral organ of abdominal cavity with multiple lobes (learn them!!) Sets against inferior surface of diaphragm on left side Forms as outpocketing of gut--common bile duct is left as connection Bile duct is two-way street (bile from hepatic duct is stored in gall bladder and later expelled to common bile duct to duodenum) FUNCTION Digestion--bile is digestive enzymes plus RBC breakdown product Removes nutrients and toxins from blood (hepatic portal system brings gut blood directly to liver) Glucose metabolism (with pancreas--see below)

General blood supply to gut--ventral branches off of aorta Celiac a.--to stomach, liver, pancreas, spleen, duodenum Superior (cranial mesenteric a.--to small intestines and most of colon Inferior (caudal) mesenteric a.--to descending colon, rectum

Liver: Blood Supply Hepatic Vein from inferior vena cava Hepatic Artery from abdominal aorta Hepatic Portal Vein Carries nutrient-rich blood from stomach + intestines to liver Portal system = 2 capillary beds! pg 660

Hepatic Portal System--anatomy

Hepatic Portal System--concept Directs blood that has already been through gut capillaries into liver capillaries (or sinusoids) Allows nutrients and toxins to be removed from blood Fig , M&M

How does liver work? Blood from portal vein and hepatic artery enter into central vein of liver lobules Leaky capillaries called sinusoids then bring blood into contact with hepatocytes or liver cells

Liver function Versatile hepatocytes do the following: Process nutrients including storage of glucose Store fat-soluble vitamins for later use by body Detoxification of blood Other macrophage-like Kupffer cells also remove debris such as worn-out RBC’s

Following a meal, with nutrients flowing into blood from gut

Role of insulin in take-up of glucose (from pancreas beta cells) by cells during absorptive state

Between meals, with no nutrients flowing into blood from gut

Role of glucagon (from pancreas alpha cells) in release of glucose by cells during post- absorptive state

Pancreas STRUCTURE Smaller, diffuse gland Head in C of duodenum Tail extends towards spleen FUNCTION Digestion--produces most digestive enzymes Glucose metabolism--Islets of Langerhans Beta cells make insulin Alpha cells make glucagon

“How Stuff Works” Diabetes: ffworks.com/diabet es1.htm

Liver receives blood from intestines (don’t forget hepatic portal system After meal, in response to insulin from pancreas, glucose stored as complex carbohydrate--glycogen--in liver Between meals, in response to glucagon from pancreas, glucose is released Pancreas releases insulin when sugar levels in blood go up Inadequate or zero insulin production results in hyperglycemia or high blood sugar Overproduction or over-dosing of insulin results in hypoglycemia or low blood sugar--insulin shock Diabetes is insufficient production of insulin Type I--juvenile onset with elimination of Islets of langerhans and zero insulin production Type II--adult onset with gradual loss of insulin production Glucose metabolism