FORM & FUNCTION (Diabetes Mellitus)

Question 1

Normal physiology: insulin

Answer 1

-binds to insulin receptor to activate GLUT4 to facilitate removal of glucose from bloodstream and into cells

Question 2

Type I diabetes: insulin

Answer 2

-insulin-dependent (deficient)
-insulin not produced by beta-cells in pancreas
-leads to inactivation of GLUT 4 and high blood glucose content (hyperglycemia) causing diabetes

Question 3

Type II diabetes: insulin

Answer 3

-noninsulin-dependent (resistant)
-cell is resistant to effects of insulin due to prolonged overproduction that desensitizes the insulin receptor
-leads to defective activation of GLUT 4 and hyperglycemia causing diabetes

Question 4

Canine DM (Type I):

Answer 4

-mostly hyperinsulinemia
>more prevalent now
>peak occurrence is 7-11 years
-multifactorial cause

Question 5

Multifactorial cause: canine DM (Type I)

Answer 5

-genetic predisposition
-obesity
-pancreatic cell destruction (ex. repeated pancreatitis from inflammation)
-endocrine disorders

Question 6

Feline DM (Type 2)

Answer 6

-mostly insulin resistant
>6x less sensitive to insulin, eventually progresses to type I
-common (1 in 50 to 1 in 400)
-multifactorial

Question 7

Multifactorial: Feline DM (Type 2)

Answer 7

-genotype (DSH, Russian Blue, Burmese, Siamese)
-obesity (4-6kg overweight: 50% decrease in insulin sensitivity)
-inactivity

Question 8

Type 2 when unmanaged:

Answer 8

-keeps producing more and more insulin, putting more of a strain on pancreatic cells
>eventually leads to self destruction which then progresses to type 1

Question 9

Conditionally-induced starvation:

Answer 9

-perceived state of CHO deprivation

Question 10

Conditionally-induced starvation: steps

Answer 10

-‘starvation in the midst of plenty’
1. Meal
2. Increase in blood glucose
3. Pancreas does not make insulin (Type I: canine) or insulin doesn’t activate GLUT4 (Type 2: feline)
4. CHO deficiency leading to starvation
*also hyperglycemia can lead to glucose toxicity

Question 11

CHO deficiency leading to starvation:

Answer 11

-steatosis
-ketoacidosis
-muscle wasting

Question 12

DM effects on glucose metabolism:

Answer 12

DM effects on glucose metabolism:
1. Decrease in insulin levels or activity
2. Increase in glucagon (pancreas): development of hyperglucagonemia
>Increase glycogenolysis in liver (glycogen phosphorylase)
>Increase gluconeogenesis in liver (PEPCK mRNA)
3. Liver increases glucose
4. Exacerbates hyperglycemia due to
>Lack of tissue uptake
>Increase in hepatic glucose production

Question 13

DM effects on lipid metabolism:

Answer 13

-healthy conditions: insulin suppress lipolysis
1. Activates phosphodiesterase (coverts cAMP to 5’AMP)
2. Activates protein phosphatase-1 (de-phosphorylate HSL)
*diabetic patients: insulin deficiency/resistance loses this control=HIGH RATE OF LIPOLYSIS

Question 14

DM effects on lipoprotein lipase (LPL):

Answer 14

1. Insulin deficiency/inactivity reduces LPL activity
2. Inadequate FFA transport into muscle (for energy) and adipose (for storage)
3. Weight loss (coupled with high lipolysis): hyperlipidemia leading to steatosis
   *even though body is releasing fat it can’t get to the tissues

Question 15

DM effects on Randle-cycle:

Answer 15

-excess FFA blocks glucose-oxidation (Randle-cycle): from the FFA released form adipose tissue
-glucose transported impaired by lack of GLUT4 activation (insulin deficiency/resistance)
*END RESULT: excess lipolysis exacerbates hyperglycemia

Question 16

DM effects on ketones:

Answer 16

1. Glucose deprivation (unable to enter cells)
2. Lack of insulin control on lipolysis
3. Glucagon stimulating gluconeogenesis
   *all leads to: continuous ketone production leading to diabetic ketoacidosis

Question 17

Ketone dipstick:

Answer 17

-urine dipstick for ketone analysis
-only detect acetoacetate and not beta-hydroxybutyrate
*quick results, but can underestimate true ketone level

Question 18

DM muscle wasting:

Answer 18

-muscle proteins begin to breakdown as starvation signal persists (atrophy)
>protein synthase (build new muscle) is impaired as it requires insulin
>proteolysis increase substrates for gluconeogenesis (hyperglycemia) and ketogenesis (ketoacidosis)

Question 19

DM induced starvation:

Answer 19

-perceived state of starvation, blood glucose continues to rise
-sequence of metabolic adjustment Is similar to starvation but the plasma glucose continues to rise