Biochem Chapter 31 Homeostatis and Fuel Metabolism: Diabetes Mellitus

What is glucose stored as?

Limited amount as glycogen

Excess converted to fatty acids

Caloric Value of fat, carbohydrate, and protein

Fat highest 9kcal/g

Carbohydrate and protein both 4kcal/g

The main substrates for gluconeogenesis are ______ derived from anaerobic glycolysis, _______ from the amino acids released during the breakdown of muscle protein, and _______ from the breakdown of triacylglycerols in the adipose tissue

lactate, alanine, glycerol

Excess amino acids taken in food are converted to _______

carbohydrates

Glucose is usually the only fuel source for brain

What is the alternative during starvation

Ketone Bodies

Gluconeogenesis occurs primarily in the _____ and, during prolonged fast, in the _____

liver, kidney

During short-term exercise, the preferred substrate for muscle is _______. However, at rest and during prolonged exercise, the main energy source is _______

glucose, fatty acids

Can myocyte convert release glucose into the circulation

No although they have glycogen, they do not have glucose-6-phosphatase

What hormone controls glucose homeostasis

What hormone act as counterregulatory hormones

Insulin

Glucagon, catecholamines, cortisol, and growth hormone

The β-cell takes up glucose using the membrane transporter _______

GLUT-2

What is GLUT-4 transporter

Insulin dependent glucose transporter in adipose tissue

Is insulin anabolic or catabolic

Insulin stimulates anabolic (synthesis)

Insulin suppresses catabolic (breakdown)

Glucose transport in muscle and ______ tissue is mediated by the GLUT-4 transporter and is insulin dependent. On the other hand, GLUT-2 present in the ______ is insulin independent.

adipose

liver

In the liver, insulin resistance results in an _______ in lipogenesis and triglyceride synthesis as well as VLDL secretion.

increase

The most important cause of insulin resistance is defective insulin ______

signaling

Glucagon and other antiinsulin (counterregulatory) hormones _______ plasma glucose concentration by stimulating glycogenolysis and gluconeogenesis

What stimulates glycogenolysis in liver and in muscle

increase

Glucagon in liver, Epinephrine in muscle

There are no glucagon receptor in muscle

What is the key hormone responsible for stress-related hyperglycemia.

Epinephrine

Incretin hormones are secreted by the gut and potentiate insulin secretion

What are example of them

GLP-1, colecystolinin, VIP

GLP-1 increase insulin secretion and decreases glucagon secretion

GLP-1 decrease gastric emptying and increase feeling of satiety

Insulin to Glucagon ratio

High insulin low glucagon is fed state

High glucago low insulin is is fasting state

Postabsorptive state and prolonged fasting

Fasting for 6-12h is postabsorptive

Longer than 12h is prolonged fasting or starvation

Insulin and glucagon switch ______ on and off during the feed–fast cycle

genes

What is Cori cycle

What is glucose-alanine cycle

Muscle produces lactate that enters bloodstream taken up by liver and oxidized to pyruvate for gluconeogensis (glucose from noncarb) and glucose is sent back to muscle

Glucose-alanine use alanine and glutamine from muscle instead of lactate in low insulin

Free fatty acid use in starvation

Beta oxidation of fatty acids generates acetyl-CoA. Normally enters TCA cycle but ongoing gluconeogenesis depletes oxaloacetate and accumulation of acetyl-CoA causes ketogenesis which can be used by brain and other muscle

The metabolic response to stress mobilizes energy substrates from all available sources; during stress, metabolism is driven by the ________ hormones

antiinsulin

Do pt suffering from burn trauma have hyper or hypometabolism

Hypermetabolism

________ is the main cause of blindness in the Western world and one of the main causes of kidney failure.

Diabetes

Longer term diabetes cause micro and macroangiopathy (change in arteries wall)

What is IFG and IGT

IFG Impaired Fasting Glucose (high glucose when fasting0

IGT Impaired glucose tolerance

Signify risk for diabetes

What is MODY and its treatment

Rare form of diabetes before age 25

Sulfonylurea drug

Is ketoacidosis in T1D or T2D

T1D (lack of insulin)

Very rare in type 2

What is smelling like acetone a sign of

Diabetic ketoacidosis

Metabolic Syndrome in Diabetes

Linked with cardiovascular disease

Dyslipidemia and arterial hypertension

Why is glucose toxic in excess

Autooxidation with copper or iron (ROS)

Hyperglycemia alters cellular redox state, It directs glucose into the polyol pathway where it is reduced to sorbitol by aldose _______

reductase

Sorbitol is osmotically active (traps water) cause diabetic cataracts

What is the most common acute complications of diabetes

Hypoglycemia or Ketoacidosis

Hypoglycemia

Require immediate glucagon injection or glucose

The measurements that are diagnostic for diabetes are the ______ plasma glucose concentration

fasting

IFG and IGT are prediabetic

FPG of 7.0 mmol/L is diagnositc for diabetes

What is OGTT

Oral glucose tolerance test

Test fasting plasma glucose first, then drink glucose and test in 2 hours

Plasma glucose too high is diabetic

The glycated hemoglobin (______) concentration reflects the average concentration of plasma glucose

HBA1c

Know if pt only complied to treatment days before testing

Can urine glucose test diabetes

No

Ketonuria in diabetic pt

Sign of metabolic decompensation and require treatment

Patients with type 1 diabetes are treated with ______

insulin

If hypoglycemia use glucagon

What ion need to be supplemented in ketoacidosis

Potassium (excreted in urine)

Acid and K are opposite

PPAR-γ is a target of ________, drugs that are used to treat T2D.

thiazolidinedione

Metformin, a _______, is currently the most common oral treatment in T2D.

Biguanide

Reduce hepatic gluconeogenesis for T2D

_________, such as pioglitazone, improve peripheral glucose utilization and insulin sensitivity.

Thiazolidinediones

Sulfonylureas vs Meglitinides

Sulfonylura bind to SUR1 on K-ATP on B cells opening Ca channel and secrete insulin

Meglitinides bind to K-ATP on B cell and increase insulin secretion (faster)

_______ receptor agonists, such as exenatide or liraglutide, increase insulin secretion

GLP-1

_______ is an inhibitor of intestinal α-glucosidase, an enzyme that digests complex sugars. It delays intestinal absorption of glucose.

Acarbose

Sodium glucose-linked cotransporter 2 (______-) inhibitors decrease glucose reabsorption in the kidney

SGLT2