Basic biochemical examination in endocrinology

Basic biochemical examination in endocrinology

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Description: Hormones are endogenous substances produced by specializeded cells. Hormones types: Proteohormones and peptides, Steroid hormones, Low molecular weight hormones derived from modified amino acids, Prostanoids. DM definition: WHO 1985- Status characterized by chronic elevation of blood glucose, that could be connected with clinical syndromes and could lead to death without proper care.

Insulin- Secretion increased: elevation of blood sugar, aminoacids, parasympaticus system action, glukagon, glucocorticoides, growth hormone, placental lactogen,estrogenes, gestagenes (during pregnancy).

 
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Contents:
Basic biochemical examination
in endocrinology
Zdislava Vaníčková
2012

Diabetes mellitus
Endocrinology of reproduction

Endocrinology

Hormones - definition
Hormones are endogenous substances produced by
specializeded cells

Secretion:

continuous (thyroid hormones)
with diurnal rhythm (cortisol)
with monatial rhythm (menstrual cycle hormones)
seasonal rhythm (parathormon)

Hormones - types
Proteohormones and peptides
Steroid hormones
Low molecular weight hormones derived from modified amino
acids
Prostanoids

Action of hormones
Autocrine
Paracrine
Endocrine

Diabetes mellitus

DM definition
WHO 1985
Status characterized by chronic elevation of blood glucose,
that could be connected with clinical syndromes and could
lead to death without proper care.

Langerhans islets

B (beta) cells
70%
Produce insulin

Insulin
Men and other mammals
1 gen on chromosome 11
(rodents, 2 genes)
51 AA, 2 strands
Homology between species high:
pig, dog, hare 1 AA; cow 3 AA; sheep, horse 4 AA.
Secretion increased: elevation of blood sugar, aminoacids,
parasympaticus system action, glukagon, glucocorticoides,
growth hormone, placental lactogen,estrogenes, gestagenes
(during pregnancy)
Secretion decreased: fats, sympaticus action, somatostatin,
adrenalin

Insulin
PREPROINSULIN

C peptid

PROINSULIN

INSULIN

Insulin
Daily production:
40-50 units
(15-20% of pancreatic depot)
50% basal secretion
50% postprandial secretion
Plasmatic halftime:
3-5 minutes, no transport protein

First-pass effect:
50% used during first passage through liver

C peptid
Function unknown
Variable length
Used as marker of endogenous insulin production
(produced in equimolar proportion, can be used in patients
on insulin therapy as well)
No first-pass effect

Insulin like growth factors
IGF-I
70 AMK
IGF-II
67 AMK

62 % homology (IGF-I and IGF-II)
50 % homology with insulin
More stimulate growth than insulin
Have less metabolic effect than insulin

A (alpha) cells
25%
Produce glucagon

Glucagon
29 amino acids
Synthetized as proglukagon
Plasmatic halftime 5 minutes
No transport protein
Inactivation in liver

Glucagon
Enhances
glycogenolysis
lipolysis
gluconeogenesis
ketogenesis
Receptors mainly in liver

D (delta) cells
5%
Produce somatostatin

Somatostatin
cyclic peptide, 14 amino acids
in CNS – neurotransmitter function
synthesized also in other places in GIT
Inhibition of insulin and glucagon secretion
Slowers gastric emptying, lowers gastrin secretion,
pancreatic exocrine secretion, …

Blood glucose regulation

FOOD INTAKE

INSULIN
glucagon like peptid
utilization in CNS
muscle work

+
GLUCAGON
catecholamins
glucocorticoides
growth hormone

Blood glucose regulation

INSULIN
glucagon like peptid
utilization in CNS
Muscle work

+
GLUCAGON
catecholamins
glucocorticoides
growth hormone

DM diagnosis
Fasting glycemia (venous and capillary blood)
7 mmol/l

no DM
impaired fasting glycemia
DM present

Glycemia in random sample
Several times >10mmol/l

DM present

DM diagnosis
OGTT (oral glucose tolerance test)
75 g of glucose in 400 ml water (tea)
Measurement at time 0 and 120 min (60 min and 180 min
sometimes added)

7.8

NORMAL

0

60

120

DM diagnosis
OGTT
Impaired glucose tolerance

11.1
7.8
repeat OGTT
every 2-3 years
0

60

120

DM diagnosis
OGTT

11.1
7.7

DM

0

60

120

DM

Insulin
secretion

glycemia

11.1
7.7
8-10 years

Insulin
sensitivity

Lab tests in DM
BLOOD GLUCOSE
fasting
random
oral glucose tolerance test (OGTT)
glycemic profile
GLYCATED HAEMOGLOBIN, PEPTIDES, AGEs
INSULIN, C PEPTID, anti-GAD antibodies, antibodies against
insulin, antibodies against B cells (ICA, IA2)

haemoglobin glycation
HC=O

ß-NH2 +

|
HCOH
|
HOCH
|
HCOH
fast
|
HCOH
|
CH2OH

HC=N-ß

CH2-NH-ß

|
|
HCOH
C=O
|
|
HOCH
HOCH
|
|
HCOH slow HCOH
|
|
HCOH
HCOH
|
|
CH2OH
CH2OH
Aldimin
(labile HbA1c)

Ketoamin
(stabile HbA1c)

Haemoglobin - types
Haemoglobin
and derivates

Subunits
present

sugar

content

HbA0

α2ß2

-

> 90%

HbA2

α2δ2

-

2%

HbF

α2γ2

-

0.5%

HbA1a1

α2(ß-F-D-P)2

HbA1a2

α2(ß-G-6-P)2

HbA1b

?

HbA1c

Fructose-1,6diphosphate
Glucose-6phosphate
?