Physio Exam One

Digestive System Overview

• Key structures:

  • Esophagus

  • Stomach

  • Gallbladder

  • Small intestine (small bowel)

  • Large intestine (colon)

  • Rectum

  • Anus

• Main functions:

  • Digestion of nutrients:

  • Carbohydrates, fats, proteins

  • Absorption and transport across cell membranes

Objectives

• Understand the major regulatory hormones regulating blood glucose.

• Identify the sources of these hormones and how they are regulated.

• Define the cellular and molecular mechanisms by which insulin regulates blood glucose.

• Compare and contrast type 1 and type 2 diabetes mellitus.

Importance of Glucose

• Glucose as a metabolic fuel:

  • Major fuel source for all tissues

  • Essential for:

  • Red blood cells

  • Renal medulla

  • Brain (under normal conditions)

  • Skeletal muscle contraction under stress ("fight or flight")

  • Carbon skeletons for synthesis of:

  • Non-essential amino acids

  • Ribose and deoxyribose

  • Triglyceride (TG) components (glycerol & fatty acids)

Regulation of Blood Glucose

• High blood glucose triggers insulin-secreting cells in the pancreas.

• Insulin functions:

  • Causes liver cells to store glucose as glycogen

  • Enhances cellular uptake of glucose

• Negative feedback mechanism:

  • As blood glucose levels decline, glucagon secretion occurs, halting insulin release.

  • Results in the return to homeostatic glucose levels until the next meal.

Blood Glucose Levels

• Typical pattern:

  • Blood glucose rises after meals

  • Insulin levels increase correspondingly

  • Reference range:

  • Normal fasting: <100 mg/dL

  • Pre-diabetic: 100-125 mg/dL

  • Diabetic: >125 mg/dL

  • Glucose can vary based on time of day and food intake:

  • 140 mg/dL post-meals, normalized before the next meal

Pancreas Overview

• Functions as both an endocrine and exocrine gland.

• Endocrine cells located in the islets of Langerhans:

  • Alpha cells: secrete glucagon

  • Beta cells: secrete insulin

Endocrine Functions of the Pancreas

• Insulin:

  • Secreted by beta cells in response to elevated blood glucose.

  • Stimulates:

  • Glycogen synthesis in the liver

  • Cellular uptake/utilization of glucose, decreasing blood glucose levels.

• Glucagon:

  • Secreted by alpha cells when blood glucose is low.

  • Functions to raise blood glucose by:

  • Stimulating glycogenolysis and gluconeogenesis in the liver

  • Increasing blood glucose levels

Mechanisms of Insulin Release

• Triggered by glucose uptake and ATP generation.

• Increase in ATP modifies membrane potential leading to insulin release.

• Proinsulin processed into active insulin, along with c-peptide via exocytosis, releasing both into the bloodstream.

Insulin Signaling Mechanism

• Insulin binds to receptors on target cells, primarily in adipose tissue and skeletal muscle.

• GLUT4 carrier proteins are mobilized to the cell membrane, allowing glucose entry through facilitated diffusion.

• This promotes glycogen storage in the liver and muscles and stimulates fat storage in adipose tissue.

Glucose and Glycogen Dynamics

• High glucose concentration necessitates GLUT mechanisms for glucose uptake:

  • Glucose diffuses until equilibrium, but glucose 6-phosphate conversion maintains lower intracellular glucose.

  • Glycogen storage ensures low intracellular concentrations, promoting continuous diffusion and preventing cellular osmosis.

GLUT Transporters

• GLUT1: Blood-brain barrier, heart, liver, pancreas

• GLUT2: Small intestine, brain, neurons

• GLUT3: Neurons

• GLUT4: Insulin-dependent uptake in adipose and skeletal muscle (increased sensitivity)

• GLUT5: Heart

Glycogenesis & Glycogenolysis

• Glycogenesis:

  • Formation of glycogen from glucose; vital for maintaining low intracellular glucose.

• Glycogenolysis:

  • Breakdown of glycogen into glucose

  • Produces glucose 1-phosphate, converted to glucose 6-phosphate; liver converts it back to glucose for blood circulation.

Glucagon's Role

• Antagonistic to insulin and raises blood glucose when levels are low.

• Functions:

  • Stimulates glycogen hydrolysis (glycogenolysis) and gluconeogenesis

  • Stimulates lipolysis to increase fat availability as an energy source.

Metabolic States - Fed vs. Fasted

Fed State

• Carbohydrates:

  • Increased glucose uptake and ATP production

  • Increased glycogenesis and lipogenesis

• Fat:

  • FA and glycerol form triglyceride storage

• Protein:

  • Amino acids used for protein synthesis; excess converted to triglycerides

Fasted State

• Carbohydrates:

  • Decreased uptake and utilization

  • Increased glycogenolysis and gluconeogenesis

• Fat:

  • Breakdown of triglycerides to FA and glycerol

• Protein:

  • Increased protein breakdown for gluconeogenesis

Diabetes Mellitus

• Characterized by chronic hyperglycemia due to insufficient insulin secretion or action.

• Major causes:

  • Kidney failure, limb amputation, blindness, heart disease, and stroke.

Classifications of Diabetes

Type 1 Diabetes (Insulin-dependent)

• Beta cells destroyed (autoimmune); insulin production ceases.

• Requires insulin injections.

• Environmental factors trigger onset:

  • Viral/bacterial infections

  • Autoreactive T cells (helper and killer)

  • Autoantibodies targeting beta cells

Type 2 Diabetes (Insulin-independent)

• Most common, linked to insulin resistance.

• Strongly associated with obesity; familial tendencies.

• Rising incidence in children due to obesity.

Insulin Sensitivity and Resistance

• Insulin Resistance:

  • Receptor fails to respond appropriately.

  • Obesity decreases insulin sensitivity, increasing required insulin production for effect.

• Results in the liver's unrestricted glucose production and lack of glucose uptake by muscles.

• Exercise promotes GLUT4 insertion in muscle cells without insulin.

Glycated Hemoglobin (A1c)

• Measures average blood glucose over months.

• Normal A1c: 5%, pre-diabetic: 5.7% - 6.4%, diabetic: >6.5%.