Diseases in Saccharide Metabolism

Insulin resistant

________ (insensitive) response- blood glucose level does not fall by 50 % or requires more than 30 min to reach the maximum hypoglycaemic level (in hyperpituitarism and adrenals)

NB

________: may be simplified by taking a single sample at 2 hr after giving glucose.

Phase

________: absorptive- the rate of glucose entry into circulation exceeds the rate of removal and the blood glucose rises.

Blood samples

________ are taken at 30- min intervals for 3 hours.

active absorption

The ________ of glucose across the intestinal mucosa is connected with phosphorylation in the mucosal cell.

Epinephrine

________ (adrenaline)- increases glucose due to stress reaction.

Starch

________ and glycogen into glucose by amylase and maltose.

fundamental defect

The ________ in diabetes mellitus: absolute or relative lack of insulin resulting in an inability to utilise glucose.

symptoms of hypoglycaemia

A 10- day- old piglet can starve up to 3 weeks before ________ occur (apathy, weakness, convulsions, coma, and death)

45 minutes

Reading: time required for the glucose concentration fall by one- half (T1 /2) is estimated between 15- ________ postinfusion from graph.

Fructosamine

________- an indicator of average blood glucose from the previous 2 weeks.

NADH

________ is determined spectrophotometrically.

Infusion

________ can be given within the time limits.

Glucose molecules

________ irreversibly bound to proteins are known as glycated proteins.

Glucagon

________- maintain physiological levels of glucose.

Glucose

________ is supplied from the liver into circulation by two metabolic pathways.

RBC

The plasma or serum must be separated from ________ within 1 /2 hour.

galactose

Glucose, ________ and fructose are principle forms of carbohydrates in which absorption occurs in monogastric animals.

membrane transfer system

The ________ is the rate- limiting in peripheral tissues which are sensitive to insulin (muscle, adipose)

HbA1c

In dog, ________ has a half- life of 60 days so it reflects the average blood glucose 2 months prior to sampling.

deficiency

Due to insulin ________, the glucose intolerance is observed in all three types of diabetes.

Plasma glucose

________ is determined in the all samples, results are plotted semilogarithmically.

intensity of green colour

The ________ is proportional to the glucose concentration and is determined spectrophotometrically.

Gluconeogenic mechanisms

________ (glucose synthesis) are underdeveloped and gluconeogenic enzymes must be induced by feeding within after birth to reach their maximal activities.

amount of NADPH

The ________ is measured spectrophotometrically and serves for calculation of glucose concentration.

Blood glucose level

________ is high enough to give a maximal insulin response.

Direct Methods

________- measurement of actual glucose concentration using spectrophotometry; adapted for use by automatic analysers.

Urinary loss of glucose

________ is minimal.

protein

When the ________ of the complex is albumin, the product is fructosamine.

Phase

________: removal of the glucose excess- the rates of removal now exceed those of entry, hepatic glucose output decreases and the blood glucose falls rapidly until it reaches baseline level.

epinephrine (adrenaline)

increases glucose due to stress reaction

glucagon

maintain physiological levels of glucose

Direct Methods

measurement of actual glucose concentration using spectrophotometry; adapted for use by automatic analysers

Indirect Methods

monitoring blood glucose methods using so-called glycated proteins

albumin

half-life 7-9 days

fructosamine

an indicator of average blood glucose from the previous 2 weeks

dog

1.7-3.38 mmol/l

cat

2.19-3.47 mmol/l

dog

a test meal consisting of 4 g glucose/kg body weight mixed with a few grams of meat

NB

may be simplified by taking a single sample at 2 hr after giving glucose

after a standard fasting (12

16 h) (overnight) a zerotime heparinized blood sample is taken

cannot tolerate extra glucose

typical diabetic type of GT curve

interpretation

normally, blood glucose level falls to 50% of its fasting level in 20-30 minutes, and returns to its fasting level in 1.5-2 hr

insulin resistant (insensitive) response

blood glucose level does not fall by 50% or requires more than 30 min to reach the maximum hypoglycaemic level (in hyperpituitarism and adrenals)

unresponsive hypoglycaemia

the hypoglycaemia is prolonged and fails to return to the fasting level in 2 hr (observed in hyperinsulinism, hypopituitarism, hypoadrenalism)

some other factors

pancreatitis, infections, stress, oestrus

the fundamental defect in diabetes mellitus

absolute or relative lack of insulin resulting in an inability to utilise glucose

Type I (loss of pancreatic β-cells)

some viral infections, autoimmune diseases

occurs in

dogs, children

in mother

agalactia, metritis

in piglet

anaemia, infections

What are the functions of saccharides?

energy source,
precursors of essential metabolites for use in synthetic processes,
components of nucleic acids and coenzymes
essential lipid metabolism

How are saccharides digested?

saliva contains amylase and maltase;
small intestine enzymes of pancreatic juice and succus entericus

What are the monomers of starch and glycogen?

glucose

What are the monomers of lactose?

glucose and galactose

What are the monomers of saccharose?

glucose and fructose

Where and how are saccharides absorbed?

mucosa of the small intestine into portal circulation by passive diffusion or sodium-dependent active transport

What does the fate of absorbed glucose depend on?

nutritional demands of the organism

What is the fate of hexoses during and after feeding?

converted to glucose by the liver and stored in glycogen or as fat

What is the fate of hexoses during fasting?

glucose is supplied from the liver into circulation by gluconeogenesis and glycogenolysis

Which are the two main hormones involved in the regulation of glycogenolysis?

epinephrine and glucagon

What are the glucose transport proteins and where are they located?

GLUT-1 (brain, RBC, placenta, kidney)
GLUT-2 (liver, pancreas)
GLUT-3 (brain)
GLUT-4 (skeletal, cardiac muscle, adipose tissue)
GLUT-5 (small intestine)

What is the role of the liver in control of glucose concentration?

at blood glucose level 8.33 mmol/l the liver does not take up or supply glucose to the circulation;
when blood glucose level is above 8.33 mmol/l glucose is stored in the liver as glycogen;
when blood glucose level is below 8.33 mmol/l glucose is supplied from the liver by gluconeogenesis and glycogenolysis

What happens when glucose is administered to a normal animal?

Phase 1: absorptive - rate of glucose entry into circulation exceeds the rate of removal and the blood glucose rises. As blood glucose rises, release of glucose from the liver is inhibited and insulin is released from the pancreas. In 30-60 minutes, the peak level of blood glucose is reached, then begins to fall;
Phase 2: removal of the glucose excess - the rates of removal now exceeds those of entry, hepatic glucose output decreases and the blood glucose falls rapidly falls rapidly until it reaches baseline level
Phase 3: hypoglycaemic phase - when blood glucose reaches baseline level, it continues to fall for a short time, then returns to baselevel

What are the direct methods of measurement of saccharides in animals?

toluidine method;
hexose kinase measurement;
glucose dehydrogenase method;
glucose oxidase method

What is the down-side to the toluidine method?

not a specific method because it detects galactose and mannose in addition to glucose (the amount of these saccharides is not significant and the values are taken as "true glucose")

Describe the hexokinase measurement

the amount of NADPH is measured spectrophotometrically and serves for calculation of glucose concentration;
glucose + ATP (hexokinase) → glucose-6-P + ADP;
glucose-6-P + NADP (glucose-6-P-dehydrogenase) → 6-GP + NADPH

Describe the glucose dehydrogenase method

the amount of NADPH is measured spectrophotometrically and serves for calculation of glucose concentration;
glucose + NAD (glucose dehydrogenase) → gluconolactone + NADH

Describe the glucose oxidase method

glucose (glucose oxidase) → gluconic acid + H2O2;
H2O2 + ABTS (peroxidase) → H2O + green colour;
the intensity of green colour is proportional to the glucose concentration and is determined spectrophotometrically

What are the indirect methods of measurement of saccharides in animals?

haemoglobin A1c (HbA1c) test; fructosamine test

What is the principles of the indirect methods of measurement of saccharides in animals?

glucose molecules irreversibly bind to proteins known as glycated proteins;
glycated proteins reflect the average blood glucose over the half-life of the protein

Describe the haemoglobin A1c test

when protein of complex glucose binds to is haemoglobin, the product is HbA1c;
in dog, HbA1c half life is 60 days;
in cat, HbA1c half-life is 40 days

Describe the fructosamine test

when protein of complex glucose binds to is albumin, the product is fructosamine;
albumin half-life is 7-9 days;
can detect changes in glucose control more quickly
colorimetric assay performed in clinical laboratory;
(dog: 1.7-3.38 mmol/l)
(cat: 2.19-3.47 mmol/l)

What are the clinical methods determination control of glucose concentration

glucose tolerance tests;
insulin tolerance test

What types of glucose tolerance tests are there?

oral glucose tolerance test (OGTT);
intravenous glucose tolerance test (IVGTT)

Describe the OGTT

fasting blood sample is taken, test meal is given, blood samples are taken at 30-min intervals for 3 hours;
interpretation: 1 hr after feeding the maximal glucose level is reached; after 2-3 hrs the glucose level returns to the fasting level

Describe IVGTT

standard fasting for 12-16 hr, blood sample is taken, 0.5g glucose/kg body weight is infused in 30s intervals;
blood samples are taken at 5, 15, 25, 35, 45, 60 mins;
interpretation: plasma glucose is determined in all samples and plotted semi-logarithmically;
reading: time required for the glucose concentration to fall by one-half is estimated between 15-45 minutes post-infusion;
normal T1/2 in dog is 25 mins, diabetic dog has a longer T1/2

How are the results of glucose tolerance tests interpreted?

animal with increased glucose tolerance has a limited rise and rapid fall in blood glucose;
animal with decreased glucose tolerance has an excessive rise with a slow return to baseline

What does the insulin tolerance test measure?

sensitivity of the blood glucose level to a test dose of insulin and the response of the animal to insulin-induced hypoglycaemia

How are the results of the insulin tolerance test interpreted?

normal: glucose level falls to 50% of its fasting level in 20-30 minutes and returns to fasting level in 1.5-2 hr;
insulin resistance response: blood glucose does not fall by 50% or requires more than 30 mins to reach the maximum hypoglycaemic level;
unresponsive hypoglycaemia: hypoglycaemia is prolonged and fails to return to the fasting level in 2 hr

When is insulin resistant response seen?

hyperpituitarism and hyperadrenalism

When is unresponsive hypoglycaemia seen?

hyperinsulinism, hypopituitarism, hypoadrenalism

What are factors predisposing diabetes mellitus?

obesity, pancreatitis, infections, stress, oestrus

What is Type I diabetes mellitus?

loss of pancreatic β-cells causing low initial insulin level and no insulin response to the administration of glucose

What is Type II diabetes mellitus?

receptor defect or deficiency causing normal to high initial level of insulin without a response to the administration of glucose

What is Type III diabetes mellitus?

characterised by normal insulin level, normal to delayed insulin response to glucose and prolonged return of insulin to normal value

What is hyperinsulinism?

persistent hyperactivity of the pancreas as the result of insulin-secreting islet cell tumours

What is hyperinsulinism characterised by?

persistent hypoglycaemia, weakness, apathy, convulsions, coma

Describe hypoglycaemia in piglets

unless the piglet is fed, its blood glucose drops rapidly to hypoglycaemic level within 24-36 hours. If the piglet suckles, its ability to withstand starvation progressively increases. A 10-day-old piglet can starve up to 3 weeks before symptoms of hypoglycaemia occur (apathy, weakness, convulsions, coma, and death);
starvation can be caused by agalactia and metritis in the mother and anaemia and other infections in the piglets

Why do piglets develop hypoglycaemia?

gluconeogenic mechanisms are underdeveloped and gluconeogenic enzymes must be induced by feeding after birth to reach their maximal activities