Biomed Systems 2- Pancreatic Hormones and Glucose Lowering Medications

Hyperinsulinemia

normal amounts of insulin are ineffective in lowering plasma glucose concentrations

glucose

... is the most important fuel for the brain

same; not altered

Brain glucose uptake occurs at the ..... rate during absorptive and post-absorptive periods and is .... in type 2 diabetes

fasting

in the .... state, insulin is low and glucagon is high

fed

in the .... state, insulin is high and glucagon is low

insulin

which pancreatic hormone:

- Anabolic;

- allows cells to take up and store glucose

glucagon

which pancreatic hormone:

- Catabolic

- causes cells to release stored nutrients (glucose) into the blood

amylin

which pancreatic hormone:

- Slows glucose absorption in duodenum

- suppresses glucagon secretion

ghrelin

which pancreatic hormone:

- Stimulates appetite,

- increases food intake and promotes fat storage

somatostatin

which pancreatic hormone:

- Decreases GI activity;

- suppresses glucagon and insulin secretion

pancreatic polypeptide

which pancreatic hormone:

- Can inhibit exocrine pancreatic secretion and gall bladder contraction,

- however it’s role in nutrient metabolism is unknown

pro hormone

insulin:

- insulin is synthesized as a ....

c peptide

insulin:

- ..... is a biomarker of endogenous insulin release

active

insulin:

- A and B chains comprise .... insulin

beta

insulin:

- Insulin secretion is stimulated when .... cells sense high glucose concentrations

promote

these neurotransmitters ... insulin secretion:

- acetylcholine

- CCK

- glucagon

- GLP-1

- GIP

inhibit

these neurotransmitters ... insulin secretion:

- somatostatin

- alpha adrenergic effects of epinephrine and norepinephrine

alpha; beta

insulin:

- each insulin receptor is composed of an ... and ... subunit

tetrameric

insulin:

- insulins receptor binds insulin to form ..... heterodrimes

phosphorylates

insulin:

- Activated insulin receptor ..... many substrates setting the signal transduction cascade in motion

GLUT1

which glucose transporter:

- Basal glucose uptake

GLUT2

which glucose transporter:

- in liver, removal of excess glucose from the blood

- in pancreas, regulation of insulin release

GLUT3

which glucose transporter:

- basal glucose uptake in brain

GLUT4

which glucose transporter:

- activity increased by insulin

- in muscle, fat, and heart

liver

effect of insulin on the ....:

- the first organ that insulin reaches though hepatic portal system

- Increases storage of glucose as glycogen

- Resets liver to the fed state by reversing:

Glycogenolysis, Ketogenesis, Gluconeogenesis

- Decreases urea production, protein catabolism

- Promotes triglyceride synthesis

- Increases potassium and phosphate uptake

adipose

effect of insulin on the ....:

- Reduces circulating free fatty acids and increases the storage of triglycerides

- Induction of lipoprotein lipase- actively hydrolyzes triglycerides from circulating lipoproteins

- Glucose transport into cells needed for esterification of fatty acids

- Reduction of intracellular lipolysis of stored triglycerides by inhibition of intracellular lipase

muscle

effect of insulin on the ....:

- Promotes protein synthesis by increasing amino acid transport and stimulating ribosomal activity

- Promotes glycogen synthesis by increasing glucose transport into the cells

pancreatic a

glucagon:

- glucagon is synthesized in .... cells

GPCR

glucagon:

- Glucagon mediates it's effects via .... receptor signaling

liver

effect of glucagon on ....:

- increase gluconeogenesis

- increase glycogenolysis

adipose

effect of glucagon on ....:

- increase lipolysis

GI Tract

effect of glucagon on ....:

- relaxation of smooth muscle

heart

effect of glucagon on ....:

- increase force of contraction

GPCR

glucagon mediates its effects via .... receptor signaling

aymptomatic

insulin:

- insulin resistance is usually .....

2

insulin:

- insulin resistance and pre-diabetes leads to type ... diabetes

MASLD

insulin:

- progressive disease often associated with obesity and insulin resistance/diabetes

- A leading cause of liver failure and liver transplantation

- Under-diagnosed due to lack of robust biomarker

- Global hepatology community changed disease name to reduce stigma among healthcare providers and patient communities

complication

diabetes:

- Periodontal disease is commonly seen in people with diabetes and is considered a .... of diabetes

insulin resistance

insulin:

- Inability of the body to respond to insulin.

insulin deficiency

insulin:

- Inability of pancreas b cells to produce/secrete insulin

1

which type of diabetes:

age of onset: any age

Ketoacidosis: common

2

which type of diabetes:

age of onset: mostly adults

Ketoacidosis: rare

HbA1c (glycosylated hemoglobin)

diabetes:

- .... is a critical biomarker for glucose

insulin response

diabetes:

- Pancreatic ..... to Glucose is Defective in Type 1 and Type 2 Diabetes

insulin

the brain does not need ... to take up glucose for fuel

independent

the fasting state is mainly insulin .....

stimulated

the postprandial state is mainly insulin ....

20 years

diabetes:

- type 1 diabetes decreases life expectancy on average by ....

30-50%

diabetes:

- type 2 diabetes decreases life expectancy on average by ....

reactive hypoglycemia

diabetes:

- too much insulin activity in nondiabetics is often due to .... in response to a large carbrich meal

diabetic ketoacidosis

what acute complication of diabetes:

- Most prevalent T1DM

- T2DM under severe stress

- low arterial pH

HHNS

what acute complication of Type 2 diabetes:

- precipitated by an infection, myocardial infarction, stroke, pancreatitis or another acute illness.

- life threatening with high mortality

- serum glucose concentrations higher than 33 mmol/l , and a resulting serum osmolarity greater than 320 mOsm/L.

- water “pulled” out of cells, including brain

stroke; heart

what chronic complication of diabetes:

- 2 out of 3 people with diabetes die from .... or .... disease.

diabetic dyslipidemia

what chronic complication of diabetes:

- High LDL,

- High TG,

- Low HDL.

- This profile is linked to increased atherosclerosis resulting in build up of plaques in the vessels within the brain, heart, and periphery.

diabetic cardiomyopathy

what chronic complication of diabetes:

- diabetes-associated changes in the structure and function of the myocardium that is not directly attributable to other confounding factors such as coronary artery disease (CAD) or hypertension.

- Often linked to left ventricle hypertrophy,

- may be linked to obesity which is often present in type 2 diabetics.

diabetic neuropathy

what chronic complication of diabetes:

- About 60-70% of people with diabetes have mild to severe forms of nervous system damage,

- More than 60% of non-traumatic lower limb amputations in the United States occur among people with diabetes

foot

complications with diabetes:

- Diabetic patients with .... problems occupy more hospital beds than do those with all other diabetic complications.

diabetic retinopathy

complications with diabetes:

- leading cause of adult blindness

glucose

diabetes treatment:

- focused on ... control

7

diabetes treatment glycemic recommendation:

- HbA1C <.....%

80-130

diabetes treatment glycemic recommendation:

- preprandial capillary plasma glucose ..... mg/dL

180

diabetes treatment glycemic recommendation:

- Peak postprandial capillary plasma glucose <....mg/dL

exercise

diabetes treatment:

- ..... is the first line therapy for prediabetes and diabetes

glut4; contraction

exercise can work as diabetes treatment when insulin doesn't because it up-regulates the uptake of glucose into skeletal muscle by .... via the .... stimulated pathway

exogenous insulin

Type 1 diabetes treatment:

- first line therapy is ...

recombinant DNA

Type 1 diabetes treatment:

- human insulin is produced by ..... technology

no

Type 1 diabetes treatment:

- can insulin be taken orally

ultralente

Type 1 diabetes treatment prolonged acting insulin preparations:

- a suspension of zinc insulin forming large particles which dissolve slowly, delaying onset and prolonging duration of action.

insulin glargine

Type 1 diabetes treatment prolonged acting insulin preparations:

- Precipitation at the injection site extends the duration of action of this preparation.

detemir insulin

Type 1 diabetes treatment prolonged acting insulin preparations:

- has a FA complexed with insulin resulting in slow dissolution.

metformin

Type 2 diabetes treatment:

- first line therapy for type 2 diabetes and prediabetes

- biguinide oral therapy

- synthesized from guanidine

- exhibits first pass extraction by liver

- Anti-hyperglycemic efficacy appears to be primarily due to reduced hepatic glucose output

- inhibits fructose-1-6-bisphophatase

hepatic; F16BP

Type 2 diabetes treatment:

- metformin primarily works by reducing ..... glucose output by inhibiting .....

sulfonylurea

Type 2 diabetes treatment:

- promote IN secretion from pancreatic β-cells

- K-ATP channel modulator

- effects on insulin release independent of blood glucose

thiazolidinediones

Type 2 diabetes treatment:

- Insulin sensitizers with no effect on GSIS

- Especially efficacious in severely insulin-resistant patients

- known activators of PPARγ

GLP1 receptor agonists

Type 2 diabetes treatment:

- Incretin mimetics with antidiabetic and weight loss efficacy

- reduce CV risk

- fixes glucagon secretion

SGLT2 inhibitors

Type 2 diabetes treatment:

- The glucose transporter SGLT2 is responsible for 90% of this glucose reabsorption

- inhibition leads to decrease glucose reabsorption

- increased urinary glucose excretion

- weight loss and reduction in blood pressure

- effects independent of insulin

- stand alone therapy

- very cardio-protective