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1. In the name of God

2. Essentials of Type 2
Diabetes Mellitus, Part 1
Presented by H. Chehrehgosha
Endocrinologist
Assistant professor
Iran, Tehran, Iran University of Medical Science, Rasoul Akram Hospital
October, 2021.

3. Basic principles
Diagnosis and classification
Management
3
Agenda

4. Basic principles
Sources of
energy during
fasting
Hormone
changes after a
meal
Role of glucose
in esterification
of FFA
Insulin and
signalling
pathways
Action of
glucagon
Glucose causes
release of
insulin
Insulin
biosynthesis
Rise in glucose
and secrete
insulin
Characteristic
defects in type
2 diabetes
Insulin
resistance and
assessment
Beta cell defect
Incretins and
role in T2DM
Glucose–
glucagon axis
Starling curve
of pancreas
Glucotoxicity

5. Regulation of
glucose homeostasis
5

6. Sources of energy
during fasting
6
①
②
③
④

7. Hormone changes
after a meal
7

8. Glucose uptake into the
pancreatic beta-cell causes
insulin release
8
(1) Glucose enters the β-cell via GLUT-
2 and is metabolized
(2) ATP causes the KATP channel to
close
(3) β-cell depolarizes
(4) Depolarization causes the voltage-
dependent calcium channels to
open Ca2+ enters the cell
(5) Ca2+ causes insulin vesicle fusion
and exocytosis

9. Insulin bound to the insulin
receptor activates two
primary signalling pathways
9
MAPK PI3K
②
①
Insulin

10. Unstimulated vs.
stimulated cell
10
GLUT-4
GLUT-4
GLUT-4
GLUT-4

11. Actions of the catabolic
glucagon receptor
11

12. Insulin-dependent glucose
uptake (GLUT-4) in
adipocytes esterifies FFA
12

13. How do fatty acids
decrease insulin sensitivity?
13

14. Insulin
biosynthesis
14

15. Insulin secretory profiles
15

16. 1. What are the two characteristic defects in type 2 diabetes?
16
https://betterbodychemistry.com/obesity/insulin-resistance-
delivery-problem-hearing-problem/

17. 2. What is insulin resistance?
17

18. 3. Can insulin resistance be organ specific?
18

19. 4. What are the clinical markers of insulin resistance?
19
>102 cm
>88 cm
>25 Kg/m2

20. 5. Which is the best test to assess insulin resistance?
20

21. 6. What are the β-cell defects in the evolution of T2DM?
21

22. 7. What are incretins?
22

23. 8. What is the role of GLP1 in glucose homeostasis?
23

24. 9. What is the incretin status in T2DM?
24

25. 10. What is glucose–glucagon axis?
25

26. 11. What is “Starling curve of pancreas”?
26
(PPG)
(FPG)

27. 12. What is glucotoxicity?
27

28. 13. What is gluco-lipotoxicity?
28

29. Summary
Glucose uptake into the pancreatic beta-cell causes insulin release
Insulin bound to the insulin receptor activates two primary signalling pathways
(MAPK and PI3K)
fatty acids decrease insulin sensitivity
Insulin resistance and beta cell disfunction
Role of incretins (GLP1 and GIP) in glucose mediated insulin secretion
Role of glucotoxicity in insulin deficiency
29

30. References
30