Nutrition- Topic 3
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Nutrition- Topic 3
CHO metabolism and diabetes
What is type II diabetes?
What are the functions of glucose?
Convert to glycogen to store energy
Converted to fat to store energy
Oxidized for energy
Precursor of amino acids C-skeleton
How do you get ketosis?
Oxidization of fatty acids without glucose
What organs use glucose for energy?
Brain, RBCs, mammary gland. getus, spermatogenesis
NOT the gut (uses AA metabolism for energy)
Can you synthesize glucose from fatty acids?
Where do we get CHO from in our diet?
Plant-based foods plus milk
What is amylose?
alpha(1-4) chains of glucose
What is amylopectin?
alpha(1-4) chains of glucose with alpha(1-6) branches
What are the three types of fibre?
Soluble, Insoluble, functional
What is soluble fibre?
Forms a gel in water, pectins (found in fruits)
What is insoluble fibre?
Have beta bonds, which we cannot digest
What is functional fibre?
Psyllium added to foods
What are the freatures of soluble fibre?
Delaus gastric emptying
Binds Cholesterol and bile acids
Fermended by colonic bacteria
What are the features of insoluble fibre?
Bulk (laxitive effect)
Delays gastric emptying
Some glycemic control
Minor fermentation by colonic bacteria
How are CHO digested?
Mouth- salivary amylase
Small intestinal lumen- pancreatic amylase, glucoamylase
Small intestinal brush border- sucrase-isomaltase, lactase
What is lactose intolerance?
Lactose not digested, reaches colon
Fermentation by bacteria- flatulence (methane, hdrogen, CO2)
Breath hydrogen test to diagnose
How is lactose intolerance tested?
Breath hydrogen test
Is lactose intolerance an immune disorder?
Not immune related
What is primary lactose non-persistance?
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
What is secondary lactose intolerane?
Caused by some injury to the small intestine
eg. Parasite infection, celiac disease, pathology, malnutrition
What is congenital lactose intolerance?
Infants, lactase-free formula (unable to digest breast milk)
Same as lactose intolerance after infancy
What is a milk allergy?
Not the same as lactose intollerance
Protein, or peptides in milk
Mast cell degranulation
Massive histamine response
Involves immune reaction
How is galactose absorbed?
SGLT-1 (sodium-glucose transport proteins) and GLUT-2
First pass removal by liver
Preferential conversion to glycogen
How is fructose absorbed?
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
How is glucose homeostasis maintained?
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
What stimulates glucose synthesis?
How is glycogen degraded?
Glycogen Phosphorylase --- glucose-1-P
glucose-6-phosphatase is only in liver- this means only the liver and kidney can make glucose from glycogen
Why can only the liver and kidney make glucose from glycogen?
Glucose-6-phosphatase (the enzyme that converts glucose-6-P into glucose) is only in the liver and kidney
What is the brains glucose requirement?
What is the hepatic glycogen availability?
What is gluconeogenesis?
production of glucose from non-carbohydrate carbon substrates
What are the precursors for gluconeogenesis?
Amino acids, pyruvate, gycerol
What stimulates gluconeogenesis?
Stimulated by glucagon and glucocorticoids when plasma glucose is low
What happens as a result of gluconeogenesis?
Protein breakdown is high
What is ketogenesis?
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)
What is ketoacidosis?
Beta-oxidation of fatty acids in absence of glucose
TCA cycle intermediates depleted for gluconeogenesis
What are the components and breakdown of total energy expenditure?
67%- Basal Metabolic Rate
10%- Diet-Induced Thermogenesis
?%- Adaptive Thermogenesis
What are the facilitative glucose transporters?
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)
How do insulin receptors interact with GLUT4?
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
Why is glucose transport important?
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
What is the Cori cycle?
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)
How does athletic performance depend on glucose?
Requireent for gucose increases with exercise intensity
: glycogen for 1-3 hours
CHO loading to maximize glycogen
What is type-I Diabetes mellitus?
Blood sugar above normal levels- spilled in the urine (glucosuria)
Cell-mediated autoimmune Beta cell distruction
5-10% of all cases of diabetes
How is T1DM diagnosed?
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%)
Simplified version of T1DM
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
What are the consequences of untreated diabetes?
No glucose in cells- Ketoacidosis
How is T1DM managed?
Insulin injections (pump, nasal, islet transplant)
Balance intake, activity, insulin
How is insulin synthesized?
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
How is insulin secreted?
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
What is the peak age of T1DM onset?
What is microangiopathy?
High glucose in some non-insulin sensitive tssues damages cells
Accumulation of AGEs (advanced glycation end products)
What is nephropathy?
Thickening of glomerulus
Results in micralbuminuria
What are the risk factors for T2DM?
Heredity- multigenic disorder
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
What happens to GLUT4 peripheral tissues in T2DM?
Low muscle glycogen
Increased muscle proteolysis for gluconeogenic AAs
What happens in the liver in T2DM?
Lipogenesis, increased VLDL
Non-alcoholic fatty liver disease
How is drug treatment used to treat T2DM?
Metformin (a biguanide)
Decrases hepatic gluconeogenesis
Increased peripheral insulin sensitivity
Increases GLUT4 mediated glucose uptake
Increases fatty acid oxidation
How does metformin work?
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
How is T2DM monitored?
Fasting plasma glucose (FPG) and insulin
Oral glucose tolerance test (OGTT)
Glycated hemoglobin (HbA1c)
What is a catabolic response to surgery?
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)
How is insulin resistance and hyperglycemia caused by neuro-endocrine response combated during surgery?
How is loss of body protein during surgery combated?