Nutrition- Topic 3

Insulin resistance

• Convert to glycogen to store energy
• Converted to fat to store energy
• Oxidized for energy
• Glycoproteins
• Precursor of amino acids C-skeleton
• Prevent Ketosis

Oxidization of fatty acids without glucose

• Brain, RBCs, mammary gland. getus, spermatogenesis
• NOT the gut (uses AA metabolism for energy)

NO

• Fibre
• Starches
• Sugars
• Plant-based foods plus milk

alpha(1-4) chains of glucose

alpha(1-4) chains of glucose with alpha(1-6) branches

Soluble, Insoluble, functional

Forms a gel in water, pectins (found in fruits)

• Hemicellulose, cellulose
• Have beta bonds, which we cannot digest

Psyllium added to foods

• Viscous gel
• Delaus gastric emptying
• Glycemic control
• Binds Cholesterol and bile acids
• Fermended by colonic bacteria
• Low GI

• Bulk (laxitive effect)
• Delays gastric emptying
• Some glycemic control
• Binds cations
• Minor fermentation by colonic bacteria

• Mouth- salivary amylase
• Small intestinal lumen- pancreatic amylase, glucoamylase
• Small intestinal brush border- sucrase-isomaltase, lactase

• Lactose not digested, reaches colon
• Fermentation by  bacteria- flatulence (methane, hdrogen, CO2)
• Osmotic diarrhea
• Breath hydrogen test to diagnose

Breath hydrogen test

Not immune related

• Decreased lactase production after weaning
• 70% of adults worldwide but varies with population
• Mutation for lactase persistance (autosomal dominance- Single-Nucleotide-Polymorphism in intron)
• Dairy farming cs malaria hypothesis

• Caused by some injury to the small intestine
• eg. Parasite infection, celiac disease, pathology, malnutrition

• Non-functioning protein
• Uncommon
• Infants, lactase-free formula (unable to digest breast milk)
• Same as lactose intolerance after infancy

• Not the same as lactose intollerance
• Protein, or peptides in milk
• IgE antibodies
• Mast cell degranulation
• Massive histamine response
• Anaphalaxis
• Involves immune reaction

• SGLT-1 (sodium-glucose transport proteins) and GLUT-2
• First pass removal by liver
• Preferential conversion to glycogen

• GLUT5 facilitated diffusion agains concentration gradient into cell
• GLUT5 or GLUT2 to exit cell
• First pass removal by liver (GLUT2)
• Rapid oxidation (faster than glucose)
• Preferential conversion to fatty acids, triglycerides

• Dietary CHO from stomach delivered to small intestine
• Glucose and other monosaccharides transported through the bloodstream to the liver
• Galactose and fructose are converted to glucose
• Blood levels of glucose maintained for brain and other body cells
• Glucose transported to muscle
• Glucose is stored as glygocen in both liver and muscle
• The glycogen stored in the liver maintains blood glucose between meals
• Muscle glycogen provides immediate energy to the muscle during exercise

Plasma glucose

• Glycogen Phosphorylase --- glucose-1-P
• Phosphoglucomutase---glucose-6-P (glycolysis)
• glucose-6-phosphatase---glucose

• BUT:
• glucose-6-phosphatase is only in liver- this means only the liver and kidney can make glucose from glycogen

Glucose-6-phosphatase (the enzyme that converts glucose-6-P into glucose) is only in the liver and kidney

120 g/day

190g/day

production of glucose from non-carbohydrate carbon substrates

Amino acids, pyruvate, gycerol

Stimulated by glucagon and glucocorticoids when plasma glucose is low

Protein breakdown is high

• Fatty acid beta-oxidation in the basence of glucose
• No anaplerosis of TCA cycle
• Causes acetyl-CoA to accumulate
• Beta-hydroxybutyrate and acetoacetate are products (ketones)
• Ketone bodies are an alternate fuel for the brain (do have negative impact)

• Beta-oxidation of fatty acids in absence of glucose
• TCA cycle intermediates depleted for gluconeogenesis
• Acetyl-CoA accumulates

• 67%- Basal Metabolic Rate
• 10%- Diet-Induced Thermogenesis
• 23%- Activity
• ?%- Adaptive Thermogenesis

SLC2A1-5- Solute carrier family 2 members 1-5

• GLUT1- RBCs, brain (blood brain barrier), kidney
• GLUT2- Liver, B-cell, kidney, smal intestine
• GLUT3- Brain (neurons)
• GLUT4- Muscle, heart, adipose tissue
• GLUT5- Small intestine (fructose transporter)

• Insulin binds to receptors starts many protein cascades
• Protein cascades result in translocation of GLUT-4 to the plasma membrane
• Influx of glucose
• Glycogen synthesis, glycolsis, and fatty acid sythesis

• Glucose-6-phosphatase is only in liver (and kidney)
• Muscle can't export glucose derived from glycogen
• Peripheral cells can't synthesize glucose from glycogen of gluconeogenic precursors

• Lactic acid cycle
• Glucose in muscle is converted to 2 pyruvate (uses 2 ATP)
• 2 pyruvate is converted to 2 lactate
• Lactate goes to liver
• 2 lactate is converted back to 2 pyruvate and back into glucose (requires 6 ATP)

• Requireent for gucose increases with exercise intensity
• Marathon: glycogen for 1-3 hours
• CHO loading to maximize glycogen

• Blood sugar above normal levels- spilled in the urine (glucosuria)
• Cell-mediated autoimmune Beta cell distruction
• Genetic predisposition
• 5-10% of all cases of diabetes

• Glucosuria/Ketonuia- urinalysis
• Fasting plasma glucose concentration >7.00mmol/L (normal 5mmol/L)
• Oral glucose tolerance test- plasma glucose >11mmol/L
• Glycated hemoglobin (hemoglobin A1c) >6.5% (normal range 3.5-5.5%)

• Stomach converts food to glucose
• Glucose enters the blood stream
• Pancreas produces little or no insulin
• Glucose unable to enter body effectively
• Glucose levels increase

• No glucose in cells- Ketoacidosis
• Hyperglycemia- dehydration

• Insulin injections (pump, nasal, islet transplant)
• Balance intake, activity, insulin

• Signal peptide is translated and translocated into the ER lumen
• Folding, oxidation and signal peptide cleavage
• ER export, Golgi transport, vesicle packaging 
• Protease clevage liberatoes C-peptide
• Carboxypeptidase E produces mature insulin

• GLUT2 allows an influx of glucose
• Glucose and respiration produce ATP
• An increase in the ATP:ADP ratio closes the K-ATP channel, causing depolarisation
• Voltage-gated calcium channels cause an influx of Ca2+ 
• Ca2+ activate insulin gene expression via CREB (Calcium responsive element binding protein)
• Exocytosis of stored insulin

puberty

• High glucose in some non-insulin sensitive tssues damages cells
• Accumulation of AGEs (advanced glycation end products)

• Thickening of glomerulus
• Results in micralbuminuria
• Dialysis, transplant

• Heredity- multigenic disorder
• Obesity (visceral)

• Stomack converts food to glucose
• Glucose enters bloodstream
• Pancreas produces sufficient insulin but it is resistant to effective use
• Glucose unable to enter body effectively
• Glucose levels increase

• Fat-based economy
• Low muscle glycogen
• Increased muscle proteolysis for gluconeogenic AAs
• Cori cycle

• Gluconeogenesis
• Lipogenesis, increased VLDL
• Non-alcoholic fatty liver disease

• Metformin (a biguanide)
• Decrases hepatic gluconeogenesis
• Increased peripheral insulin sensitivity
• Increases GLUT4 mediated glucose uptake
• Increases fatty acid oxidation

• Metformin activates AMPK (AMP activated protein kinase)
• AMPK increases muscle glucose transport and decreases hepatic glucose production
• AMPK can also decrease acetyl-CoA carboxylase activity, hence decreasing hepatic FA, VLDL synthesis and increasing hepatic FA oxidation
• AMPK also decreases SREMP-1 expression and activity, which results in a decrease in hepatic gene expression and also leads to a decrease in hepatic FA, VLDL synthesis
• All of these pathways resul in a decrease in plasma glucose and plasma triglycerides

• Urinalysis
• Fasting plasma glucose (FPG) and insulin
• Oral glucose tolerance test (OGTT)
• Glycated hemoglobin (HbA1c)

• Inflammatory response and neuro-endocrine response can lead to insulin resistane and hyperglycemia
• Insulin resistance and hyperglycemia lead to loss of body protein
• Loss of body suppression can lead to immunosuppression (delayed wound healing) or muscle wasting (delayed convalescence)

Epidural analgesia

Proper nutrition