Digestion & Metabolism 2: Diabetes Mellitus Flashcards
the RIGHT LOBE of the pancreas is located in the…
the LEFT LOBE of the pancreas is located in the…
RIGHT = MESODUODENUM
LEFT = GREATER OMENTUM
when the PANCREAS is INFLAMED (pancreatitis), it can cause signs from WHAT 2 regions?
- UPPER GI SIGNS
- COLITIS (can still reach LI via TRANSVERSE COLON)
2 components of PANCREAS?
which is MAJORITY/WHAT DOES IT DO?
- MAJORITY is EXOCRINE
- ISLETS of LANGERHANS
2 main FUNCTIONS of pancreas?
in the SECOND one, list WHAT CELLS perform this function & 4 THINGS it makes!
- EXOCRINE pancreas = secretes DIGESTIVE ENZYMES & BICARBONATE
- ENDOCRINE PANCREAS via ISLETS OF LANGERHANS = secretes HORMONES, such as…
- INSULIN
- GLUCAGON
- SOMATOSTATIN
- PANCREATIC POLYPEPTIDE
ISLETS of LANGERHANS…
contains WHAT 4 kinds of cells? what does each kind make?
- ALPHA CELLS = GLUCAGON
- BETA CELLS = INSULIN
- DELTA CELLS = SOMATOSTATIN
- F CELLS = PANCREATIC POLYPEPTIDE
insulin is synthesized as a ____-___- HORMONE
has WHAT 3 components that make it up?
AFTER insulin is synthesized ___ ___ is CLEAVED OFF, leaving only WHAT 2 components for its ACTIVE form?
insulin synthesized as a PRE-PRO-HORMONE
made up of A, B & C CHAIN
after synthesis, C CHAIN CLEAVED OFF, so only A & B CHAIN LEFT in active form
the C PEPTIDE is secreted in ___ amounts to INSULIN, why?
why is this a HELPFUL parameter?
when insulin is ADMINISTERED….
EQUAL, because INSULIN ENDOGENOUSLY produced WITH C CHAIN, but CLEAVED OFF upon activation
HELPFUL parameter because it can be HARD to measure transient levels of insulin in the body, but presence of C CHAIN would indicate ENDOGENOUS INSULIN presence!
when insulin is ADMINISTERED, only A & B CHAIN are on it (since it’s active), so STILL NO C CHAIN WOULD BE DETECTED
INSULIN function…
anabolic/catabolic
= functional definition
ANABOLIC
= takes CARBOHYDRATES, AMINO ACIDS & FATTY ACIDS after we eat MEALS and STORES THEM AS GLYCOGEN, FAT & PROTEIN
INSULIN effect on GLUCOSE? (3)
- pushes glucose from BLOOD –> MUSCLE & ADIPOSE CELLS
- increases GLYCOGEN SYNTHESIS IN LIVER
- STIMULATES GLUCONEOGENESIS
GLUCONEOGENESIS…
= definition?
what HORMONE promotes this?
= the FORMATION of GLUCOSE from AMINO ACIDS
promoted by INSULIN
KETOGENESIS…
ketones are an ____ form of energy from ___
= definition?
ketones are an EXPENSIVE (energy wise) form of ENERGY from FAT
= BREAKING DOWN FATS TO MAKE KETONES FOR ENERGY
INSULIN effect on PROTEIN? (3)
- pushes AMINO ACIDS INTO MUSCLE
- INCREASES PROTEIN SYNTHESIS in MUSCLE & LIVER
- DECREASES PROTEIN CATABOLISM in MUSCLE
INSULIN effect on FAT? (4)
- INCREASES LIPID SYNTHESIS in ADIPOSE TISSUE
- DECREASES KETOGENESIS
- ACTIVATES LIPOPROTEIN LIPASE
- INHIBITS HORMONE-SENSITIVE LIPASE
LIPOPROTEIN LIPASE
located in ___
= function?
anabolic/catabolic?
___ by INSULIN
located in CAPILLARIES
= TAKES FATTY ACIDS FROM BLOOD & STORES THEM AWAY
ANABOLIC
STIMULATED by INSULIN
HORMONE-SENSITIVE LIPASE…
= function?
anabolic/catabolic?
___ by INSULIN
= takes STORED FAT & LYSES THEM to MAKE KETONES/ENERGY
CATABOLIC
INHIBITED by INSULIN
besides affecting FAT, PROTEIN & CARBS, insulin can… (2)
- INCREASES CELL GROWTH
- increases UPTAKE of K, Mg, + P into CELLS
COUNTER-REGULATORY HORMONES…
alternative NAME to COUNTER-REGULATORY?
what are the 4 names?
what DOES it counter? (2, hormone & process)
alternative name? = DIABETOGENIC (INCREASES blood glucose)
4 names?
1. GLUCAGON
2. GCCs
3. CATECHOLAMINES
4. GROWTH HORMONE
it counters INSULIN-INDUCED HYPOGLYCEMIA
4 FUNCTIONS of GLUCAGON?
anabolic/catabolic?
4 functions?
1. INCREASES GLYCOGENOLYSIS
2. INCREASES LIPOLYSIS
3. INCREASES KETONE BODY FORMATION
4. INCREASES GLUCONEOGENESIS
CATABOLIC
which out of the FOUR DIABETOGENIC hormones are the MOST EFFECTIVE & why?
GLUCAGON because it COUNTERACTS INSULIN on ALL 3 fronts: CARBS, FATS & PROTEIN
____ ____ from ____ ____ are needed to form KETONES
FATTY ACIDS, FAT BREAKDOWN
in the FED state = INSULIN/GLUCAGON dominates
in the FASTED state = INSULIN/GLUCAGON dominates
FED state = INSULIN dominates
FASTED state = GLUCAGON dominates
SODIUM-GLUCOSE COTRANSPORTER TYPE 1 & 2 (SGLT 1 & 2)
SGLT1 is located…
SGLT2 is located…
which one is MORE clinically significant?
SGLT 1 located in INTESTINE
SGLT 2 located in the PROXIMAL RENAL TUBULES
SGLT2 MORE CLINICALLY SIGNIFICANT
if SGLT1 IS DYSFUNCTIONAL, patients usually present with ___ because they CANNOT absorb ____
D+, GLUCOSE
SGLT2…
located in WHAT organ?
= function?
if it is DYSFUNCTIONAL, expect WHAT clinical sign?
located in KIDNEYS
= responsible for REABSORPTION of GLUCOSE that might’ve SPILLED INTO URINE
if DYSFUNCTIONAL, then GLUCOSURIA
SGLT2 INHIBITORS cause….
for treatment of…
cause GLUCOSE to be SPILLED OUT INTO URINE
for treatment of DIABETES MELLITUS
if a GLUCOSE TRANSPORTER is located in NEURONAL TISSUE or PLACENTA, they have ____ affinity for glucose
if a GLUCOSE TRANSPORTER is located in BETA CELL (in pancreas), they have a ____ affinity for glucose. why?
NEURONAL TISSUE or PLACENTA = HIGH affinity for glucose!
BETA CELL in PANCREAS = LOW affinity for glucose
when glucose enters BETA cell in pancreas, STIMULATES INSULIN SECRETION, but we ONLY WANT THIS WHEN GLUCOSE IS ABOVE A CERTAIN THERSHOLD; if BETA cells were to have a HIGH affinity for glucose, then could cause HYPOGLYCEMIA
DIABETES means =
MELLITUS means =
DIABETES = POLYURIA
MELLITUS = SWEET
TYPE 1 DIABETES MELLITUS
____-DEPENDENT because…
usually occurs in ____ patients
often _____-mediated
NOT associated with…
dogs vs. cats?
INSULIN-DEPENDENT because PATIENTS REQUIRE EXOGENOUS INSULIN tx
usually occurs in YOUNG patients
often IMMUNE-MEDIATED
NOT associated with OBESITY
MOST COMMON CAUSE IN DOGS & maybe CATS
TYPE II DIABETES MELLITUS
____-DEPENDENT because
usually occurs in ____ patients
often ____-associated
dogs vs. cats?
NON-INSULIN DEPENDENT because tx MIGHT NOT REQUIRE INSULIN, such as SGLT2 inhibitors
usually occurs in OLDER patients
often OBESITY-associated
NOT SUPER COMMON IN DOGS/CATS
TYPE 1 DIABETES associated with DESTRUCTION of…
REQUIRES….
etiologies? (4)
DESTRUCTION of BETA CELLS, which causes NO INSULIN TO BE PRODUCED
REQUIRES INSULIN TREATMENT
etiologies?
1. GENETIC
2. IMMUNE-MEDIATED
3. INFECTIOUS
4. TOXIC
which GENES’ altered function could be responsible for TYPE 1 DIABETES MELLITUS?
what do they code for? what do these molecules do?
in TYPE 1 DIABETES, these molecules…
what SPECIES does this occur in? what SPECIES does this process (likely) NOT occur in?
MHC genes
code for HLA CLASS 2 PROTEINS, which BIND TO ANTIGENS & PRESENT TO T CELLS to be CLEARED
in TYPE 1 DIABETES, HLA CLASS 2 PROTEINS ERRONEOUSLY PRESENT PROTEINS in BETA CELLS to T CELLS & invoke IMMUNE RESPONSE & DESTRUCTION OF BETA CELLS
HOWEVER THIS OCCURS IN HUMANS, (likely) NOT DOGS!
2 breeds at INCREASED RISK for TYPE 1 DIABETES MELLITUS?
what REGION & SEASON do dogs tend to develop TYPE 1 DIABETES?
2 breeds?
1. SAMOYEDS
2. AUSTRALIAN TERRIERS
common in NORTHERN US & WINTER in TYPE 1
TYPE 2 DIABETES MELLITUS…
commonality in DOGS/CATS?
CHARACTERIZED BY what 2 problems? which one is WORSE?
what +/- might be present/necessary? (2)
3 causes?
RARE in dogs, UNCOMMON in cats
CHARACTERIZED BY…
1. INSULIN RESISTANCE –> WORSE
2. IMPAIRED INSULIN SECRETION
+/- BETA CELL DESTRUCTION
+/- INSULIN TREATMENT/CONCENTRATION
causes?
1. GENETIC predisposition
2. OBESITY
3. AMYLOID DEPOSITION
what is the MOST COMMON reason for INSULIN RESISTANCE?
what TYPE of DZ do we expect to see this?
OBESITY
expect to see this in TYPE 2 DIABETES MELLITUS
why might insulin be HIGH in TYPE 2 DIABETES in an OBESE DOG?
if there’s INSULIN RESISTANCE due to OBESITY, then pancreas MIGHT BE MAKING MORE AND MORE INSULIN to try and compensate FOR IT NOT WORKING
OVERWEIGHT cats are ____X MORE likely to develop ____ ____ DIABETES MELLITUS
cats that go OUTDOORS are ____ likely to develop DIABETES than INDOOR cats
4X, TYPE 2
LESS
FELINE WEIGHT GAIN can be associated with WHAT 2 BIOCHEMICAL PROCESSES?
if the body returns to a NORMAL weight, then…
why is it HARDER to get CATS to LOSE WEIGHT?
WEIGHT GAIN…
1. HYPERGLYCEMIA
2. INCREASED INSULIN SECRETION
if body returns to a NORMAL weight, then BOTH CAN BE REVERSIBLE
harder for CATS to lose weight because IF THEY DON’T EAT ENOUGH, then CAN GET HEPATIC LIPIDOSIS
AMYLOID DEPOSITION…
can be a CAUSE for ___ ___ DIABETES MELLITUS, but ONLY IN ____ and NOT ____
can be a ___ finding, but MOST have ____
synthesized from ___ ____ ___
after amyloid deposition, causes WHAT 3 PATHOLOGIC CHANGES?
TYPE 2, DOGS, CATS
can be a NORMAL finding in CATS, but MOST have DIABETES
synthesized from ISLET AMYLOID POLYPEPTIDE
after amyloid deposition, causes…
1. BETA CELL DESTRUCTION
2. DECREASED INSULIN SECRETION
3. INCREASED INSULIN RESISTANCE
AMYLOID can BEHAVE DIFFERENTLY depending on…
DO NOT see ANY AMYLOID ACCUMULATION if… & this is true in WHAT species?
depending on AMINO ACID SEQUENCE
DO NOT see ANY AMYLOID ACCUMULATION if SERINE in position 28 is SUBSTITUTED for PROLINE & this is true in RODENTS
dogs will ONLY develop PANCREATIC AMYLOID DEPOSITION when associated with WHAT disease?
INSULINOMA
4 CAT breeds associated with DEVELOPMENT OF DIABETES MELLITUS?
- NORWEGIAN FOREST
- BURMESE
- RUSSIAN BLUE
- ABYSSINIAN
SECONDARY DIABETES MELLITUS…
this is SEPARATE from WHAT OTHER TWO DISEASES?
can develop in DOGS due to.. (2)
can develop in CATS due to…
in ALL of these cases, EXCESS ___ causes INCREASED ____ ____ which causes ____ ____
SEPARATE from TYPE 1/TYPE 2 DIABETES
DOGS
1. DIESTRUS
2. PREGNANCY
CATS
1. given MEGESTROL ACETATE (for CONTRACEPTION, not in US)
in ALL of these cases, EXCESS PROGESTERONE causes INCREASED GROWTH HORMONE which causes INSULIN RESISTANCE
TRANSIENT diabetes mellitus…
commonality in DOGS/CATS?
why is this CHALLENGING/DANGEROUS?
RARE in DOGS, UNCOMMON in CATS
CHALLENGING/DANGEROUS because if we’re giving INSULIN when the patient doesn’t need it, can be LETHAL (HYPOGLYCEMIC)
2 MAIN reasons for TRANSIENT DIABETES MELLITUS?
- SUBCLINICAL DIABETES that’s STIMULATED by CONCURRENT DZ that causes STRESS or ADMINISTRATION of EXOGENOUS COUNTER-REGULATORY HORMONE
- GLUCOSE DESENSITIZATION
GLUCOSE TOXICITY/DESENSITIZATION…
commonly associated with WHAT kind of diabetes mellitus?
= how does it work? & GIVE A SPECIFIC NUMERICAL PARAMETER
commonly associated with TRANSIENT DIABETES MELLITUS
= at HIGH concentrations of GLUCOSE (>540 mg/dL) can INHIBIT INSULIN SECRETION from the PANCREAS when it should NORMALLY BE SECRETED
SUBCLINICAL diabetes mellitus…
usually presents as WHAT kind of diabetes mellitus?
pathogenesis? (4)
usually presents as TRANSIENT DIABETES MELLITUS
pathogenesis?
1. patient likely has SUBCLINICAL DIABETES
- then has CONCURRENT DZ that causes STRESS & release of COUNTER-REGULATORY HORMONES or we’ve GIVEN IT a COUNTER-REGULATORY HORMONE via STEROID
- this pushes cat INTO DIABETES (–> NOT ENOUGH INSULIN and BLOOD SUGAR TOO HIGH)
- but, if we TREAT DISORDER or TAKE OFF OF DRUG, then PANCREAS can PRODUCE NORMAL INSULIN, and combined with EXOGENOUS insulin –> HYPOGLYCEMIA
TRUE/FALSE
insulin treatment is needed in VIRTUALLY ALL DOGS with DM
TRUE
TRUE/FALSE
TRANSIENT diabetes mellitus is COMMON in cats
FALSE, STILL UNCOMMON
UNCOMPLICATED diabetes mellitus in DOGS…
1. age range?
- 3 breeds at INCREASED risk?
- 3 breeds at DECREASED risk?
- what breed tends to have CONGENITAL form of diabetes?
- SEX at increased risk?
- 7-9 YEARS OLD
- INCREASED RISK = SAMOYEDS, TOY POODLES, PUGS
- DECREASED RISK = GERMAN SHEPHERDS, GOLDEN RETRIEVER, PITBULLS
- CONGENITAL FORM = KEESHUND
- FEMALES at increased risk
2 forms of COMPLICATED diabetes mellitus?
- DIABETIC KETOACIDOSIS
- HYPEROSMOLAR NONKETOTIC DIABETES MELLITUS
what is the MOST COMMON presentation of DIABETES MELLITUS in SMALL ANIMALS?
UNCOMPLICATED!
UNCOMPLICATED diabetes mellitus in CATS…
- MEAN age?
- SEX at increased risk? intact or not?
- 10 YEARS
- NEUTERED MALES
why does PU/PD occur in DIABETES? (2)
what is the RENAL THRESHOLD?
–> parameters for DOGS & CATS?
- GLUCOSE EXCEEDS capacity of SGLT2 to REABSORB GLUCOSE from URINE
- glucose SPILLS INTO URINE & acts as an OSMOTIC AGENT = POLYURIA
RENAL THRESHOLD = the CONCENTRATION of GLUCOSE that, if EXCEEDED, will cause glucose to SPILL INTO THE URINE
–> DOGS = 180 mg/dL
–> CATS = 280 mg/dL
why do animals have WEIGHT LOSS in DIABETES? (2)
- ANABOLIC hormone INSULIN is NOT WORKING, so the body is in a CATABOLIC STATE
- that means BREAKING DOWN MUSCLE & FAT
why do animals have POLYPHAGIA in DM? (2)
- because GLUCOSE is NOT BEING PUSHED INTO CELLS = STARVING
- also SATIETY signal is NOT BEING SENT
____ with diabetes can sometimes present with a ____ STANCE
___ with diabetes can present with BLINDNESS
CATS, PLANTIGRADE
DOGS –> BLINDNESS
TRUE/FALSE
on PE, diabetes patients can be NORMAL and the BODY WEIGHT can be NORMAL, OBESE, or UNDERWEIGHT
TRUE
if diabetes is caught EARLY-ON, patients can appear…
UNDERWEIGHT
GLUCOSURIA DIFFERENTIALS… (2)
- DIABETES
- TUBULAR DEFECT
DIABETIC PERIPHERAL NEUROPATHY is more common in DOGS/CATS
CATS
we would expect HYPO/HYPERCHOLESTEROLEMIA in DIABETES
HYPOCHOLESTEROLEMIA
