Glucose Metabolism Flashcards
1
Q
What are the 4 cell types in the islets of langerhans?
A
Alpha cells
Beta cells
Delta cells
F cells
2
Q
Where is insulin produced?
A
Beta cells
3
Q
Where is glucagon produced?
A
Alpha cells
4
Q
Where is somatostatin produced?
A
Delta cells
5
Q
Where is pancreatic polypeptide produced?
A
F cells
6
Q
T/F: Insulin AA sequence is preserved across species?
A
True
7
Q
What 4 things stimulate insulin secretion?
A
Rise in blood glucose
GI hormones
AA and fatty acids in GIT
Vagal (catecholamines on B2 receptors)
8
Q
What 3 things inhibit insulin secretion?
A
Decrease in blood glucose
Somatostatin
Catecholamines (a2 or I3 receptors)
9
Q
What are the 4 effects of insulin?
A
Storage and building (glycogenesis, lipogenesis, protein synthesis)
Inhibits glycogenolysis, gluconeogenesis, lipolysis
Stimulates uptake of K into cells
Anabolic
10
Q
What 3 organs metabolize insulin?
A
Liver
Kidneys
Muscle
11
Q
What causes hypoglycemia?
A
Too much insulin
12
Q
What are 5 differentials for hypoglycemia?
A
Artifact Unable to make glucose Excessive consumption Exogenous hypoglycemic agents** Endogenous hypoglycemic agents**
**care most about these
13
Q
How can hypoglycemia be an artifact?
A
If blood sample sits out for more that 30 minutes, RBCs consume the glucose in the sample.
14
Q
What are two causes of excessive consumption of glucose?
A
Sepsis
Extreme exertion
15
Q
What is an example of an exogenous hypoglycemic agent?
A
Insulin overdose
16
Q
What is an example of endogenous hypoglycemic agent? (4 things)
A
Xylitol toxicity
Insulinoma
Extrapancreatic neoplasia
Islet cell hyperplasia
17
Q
What 2 things do you consider if hypoglycemia does not involve insulin?
A
Give dextrose
Treat underlying disease
18
Q
What 2 things do you consider if hypoglycemia involves insulin?
A
If iatrogenic: stop insulin and give supportive care
If endogenous: treat hypoglycemia, then treat underlying disease
19
Q
What are the main 3 pharmacologic therapies for hypoglycemia?
A
Replacement
Diet
Anti-hypoglycemic agents
20
Q
What two things can you use to replace glucose?
A
Glucagon (not commonly used)
Dextrose
21
Q
What 2 things must you consider when using dextrose?
A
Hyperosmolality/irritation
Rising glucose stimulates insulin secretion
22
Q
What is the acute dose of dextrose?
A
1mL/kg of 50%, diluted 1:4
23
Q
What is the maintenance dose of dextrose?
A
2.5-5% dextrose IV
24
Q
Using dietary management, what do you use to treat acute hypoglycemia?
A
Karo syrup/corn syrup
25
Using dietary management, what 4 things do you use to treat hypoglycemia?
Frequent, small meals
Complex carbs
Easily digestible
Moderate fat and protein
26
What 4 pharmacologic agents can you use to treat hypoglycemia?
Glucocorticoids
Diazoxide
Streptozotocin
Somatostatin
27
What is the goal of hypoglycemia therapy?
To eliminate/minimize clinical signs associated with hypoglycemia
28
What are the two glucocorticoids used?
Predisone
| Prednisolone
29
How do glucocorticoids treat hypoglycemia? (3 things)
Increase gluconeogenesis
Decrease glucose uptake into tissue
Stimulate glucagon secretion
30
Where are glucocorticoids metabolised?
Liver
31
What two things can impair glucocorticoid metabolism?
Cirrhosis
| Shunt
32
What is important to know about glucocorticoid side effects?
They are proportional to the dose (low dose = mild, higher doses = worse)
33
When would you use Diazoxide?
If glucocorticoids and diet are no longer working
34
What are the two most common side effects of Diazoxide?
Hypersalivation
| Anorexia, V&D
35
What are 4 less common side effects of Diazoxide?
Tachycardia
Hematologic changes
Diabetes
Fluid retention
36
How does Diazoxide treat hypoglycemia?
Activates K+ channels in islet cells and switches off voltage-gated Ca2+ channels to inhibit release of insulin
37
What are two other effects of Diazoxide?
Increases glycogenolysis in the liver
| Inhibits tissue uptake of glucose
38
T\F: Diazoxide alters the synthesis of insulin and treats the neoplasia.
False. Diazoxide does not alter the synthesis of insulin or treat the neoplasia
39
How does somatostatin help treat hypoglycemia?
Inhibits the release of insulin, glucagon, GH, CCK, Secretin, Gastrin, VIP
40
What is Octreotide?
A somatostatin analogue
41
What is Octreotide used for? (4 things)
Insulinomas
Gastrinomas
Chylothorax
Acromegaly
42
How does Streptozotocin help with hypoglycemia?
Selectively destroys beta cells
43
T/F: Stretozotocin has a wide therapeutic index.
False. Streptozotocin has a very narrow safety margin
44
What causes hyperglycemia?
Too little insulin
45
What are the two differentials for hyperglycemia?
Physiologic hyperglycemia
| Diabetes mellitus
46
What is Type 1 Diabetes Mellitus?
Insulin Dependent (IDDM) = absolute deficiency of insulin
47
What is Type 2 Diabetes Mellitus?
Non-Insuline Dependent (NIDDM) = Relative insulin deficiency and resistance
48
What species do you not generally see Type 2 Diabetes in?
Dogs
49
What species can you see Type 2 diabetes in?
Cats
| Horses
50
What 3 things does insulin stimulate?
Glycogenesis
Lipogenesis
Protein synthesis
51
What 3 things does insulin inhibit?
Glycogenolysis
Gluconeogenesis
Lipolysis
52
What does lack of insulin cause in the cells?
Cellular starvation
53
What does cellular starvation entail?
Decreased tissue use of glucose
Stimulation of liver glycogenolysis
Proteolysis > AAs > gluconeogenesis
Lipolysis > FFAs > ketoacidosis > hepatic lipidosis
54
What are the 4 cardinal signs of diabetes?
Catabolism (muscle/weight loss)
Accumulation of glucose in the blood (exceeds renal tubular absorption)
Glucose in urine (see osmotic diuresis... PU/PD)
Polyphagia (lack of glucose entering "satiety center")
55
What are the 4 goals of hyperglycemia therapy?
Reduce hyperglycemia
Reverse Catabolic effects
Reverse ketosis
Control clinical signs
56
Why do you aim to maintain a hyperglycemic patient in a mild hyperglycemic state instead of a normoglycemic state?
Risk causing hypoglycemia becaues animal can't grab a snack like we can.
57
What are the three main treatments for diabetes mellitus?
General management
Diet
Pharmacological management
58
What are 2 forms of general diabetes management?
Weight management
| Exercise
59
How do we manage diabetes mellitus in dogs using diet?
Use high fiber diet
60
How do we manage diabetes mellitus in cats using diet?
Use low carb diet
61
T/F: Acarbose is a hypoglycemia agent.
False, Acarbose is NOT a hypoglycemic agent
62
How does Acarbose work to treat hyperglycemia?
Inhibits alpha amylases and brush border oligo/disaccharides to reduce postprandial hyperglycemia after CHO intake
63
What side effects can you see with Acarbose? (2 things)
Diarrhea
| Weight loss
64
What are the three classes of oral hypoglycemics?
Sulfonylureas
Biguanides
Thiazolidinediones
65
Which oral hypoglycemics are secretagogues?
Sulfonylureas
66
Which oral hypoglycemics are sensitizers?
Biguanides
| Thiazolidinediones
67
What is the most commonly used sulfonylurea?
Glipizide
68
How does glipizide stimulate insulin secretion?
Blocks potassium channels and increases Ca2+
69
On top of stimulating insulin secretion, what else does Glipizide do?
Increases sensitivity of tissues to circulating insulin
70
What does glipizide require to be functional for it to work?
Beta cells
71
How do biguanides (metformin) help treat hyperglycemia?
Inhibit hepatic glycogenolysis and increase peripheral glucose utilization
72
Does metformin affect insulin secretion?
No
73
How do thiazolidinediones (Rosiglitazone) help treat hyperglycemia?
```
PPARy agonists (receptor that regulates FA storage and glucose metabolism)
Controls glucose production, transport and utilization
```
74
What side effects can you see with Rosiglitazone?
Hepatic and cardiovascular side effects
75
What 4 questions do you ask yourself when deciding between insulin or glipizide?
Which will be more effective? (Type 2 or Type 2? Dog or cat?)
Which one is safer? (neither is safer)
Which is easier to give? (Tablet vs. injection)
Which needs less monitoring?
76
What type of diabetes are oral hypoglycemics only useful in?
Type 2 (NIDDM)
77
How effective are oral hypoglycemics?
~20-30% of cats
78
What are 4 major side effects of oral hypoglycemics?
Hypoglycemia
Vomiting
Elevated liver enzymes
May accelerate loss of beta cells
79
What are the 5 different types of insulin?
```
Recombinant human (incl. Prozinc*)
Synthetic insulin
Purified porcine (incl. Caninsulin*)
Purified bovine
Bovine-porcine
```
*approved for use in animals
80
What concentration are veterinary approved products available in?
40IU/mL
81
What concentration are human products available in?
100IU/mL
82
What 5 things must you remember about handling insulin?
```
Refrigerate
Roll gently to reconstitute
Don't dilute
Use appropriate syringe
Pay attention to expiration date
```
83
What are short-acting insulins mmost commonly used for?
Diabetic ketoacidosis (DKA) management in hospitla (CRI)
84
Why are short-acting insulins not sent home?
Duration is too short
85
What is the duration of intermediate-acting insulins?
~4-24 hours
86
T/F: Caninsulin falls under intermediate-acting insulin category.
True
87
What must be considered in cats with intermediate-acting insulins?
May not provide adequate duration.
88
What are 3 examples of long-acting insulin?
Protamine zinc
Glargine
Detemir
89
What is the reason for adding Protamine or Zinc to insulins?
Delays absorption and extends clinical effect
90
What is the duration of long-acting insulins?
6-28 hours
91
What does glargine cause?
pH causes microprecipitates
92
What is the insulin dose for dogs?
0.25-0.5IU/kg BID
93
What is the insulin dose for cats?
1IU/cat BID
94
What is the exception to the general insulin dose and why?
Detemir, because canine receptors are 4x more sensitive than human receptors (Detemir has human dose on bottle)
95
What is the does of Detemir for dogs?
0.1-0.2 IU/kg BID
96
What do you monitor when treating with insulin?
Blood glucose
Fructosamine
Clinical signs
97
How do you monitor blood glucose?
Glucose curve
98
What does fructosamine give you?
Idea of "average" glucose level
99
What is a "healthy" DKA?
Animal is eating. Can be managed like a normal diabetic, but with close monitoring.
100
What is a "sick" DKA?
Animal is not eating
101
How do you handle a "sick" DKA? (3 things)
Correct fluids/electrolytes/acid-base
Supplement K+
IV CRI of insulin to start
102
What is the goal with treating a "sick" DKA?
To reverse metabolic situation
103
What do you do with a hyperosmolar nonketotic diabetic? (2 things)
Treat like a DKA, but bring glucose down VERY SLOWLY
| Can start on fluids (no insulin) initially
104
What is insulin resistance?
Hyperglycemia despite insulin dose of 2.2IU/kg or greater
105
Can concurrent disease cause insulin resistance?
Yes
106
Can insulin autoantibodies cause insulin resistance?
Yes.
107
What is the Somogyi response?
An over dose problem where significant drop in blood glucose triggers a glucagon/epinephrine response = overswing.
