Insulin is protein hormone with 51 amino acids. It is very important hormone in the human body that regulates blood sugar level. Excess and deficiency of insulin leads to many long lasting abnormalities. Diabetes is one of biggest problem of this era. According to latest survey Pakistan rank first in the Diabetes Mellitus. Insulin also play many other functions other than regulating blood sugar. It affects on the whole physiology of the body.

1. UNIVERSITY OF CHAKWAL, PAKISTAN
1

2. Topic: Abnormalities Related To Insulin
Excess And Deficiency
Presented By: Saleha Asawar
Reg No: 20M-UOC/ZOL-38
Session: 2020-2024
BS Zoology
Subject: Endocrinology
Instructor Name: Dr. Syeda Nadia Ahmad
Department of Zoology
2

3. 3

4. INTRODUCTION
• Insulin is the protein hormone that regulates blood sugar level.
• Secreted by the beta cells of Islets of Langerhans in Pancreas.
• Secreted when blood glucose level is high.
• Secretion stops when blood glucose level is low from normal.
• First reported in pancreatic extract in 1921. (Ostergaard etal, 2020).
4

5. HISTORY
• Identified by Canadian scientists Frederick banting and Charles
best and by Romanian physiologist Nicolas C. Paulescu.
• After banting and best isolated insulin, they began work to obtain a
purified extract, which they accomplished with the help of Scottish
physiologist J.J.R. Macleod.
• Canadian chemist James B. Collip. banting and MacLeod shared the
1923 Nobel prize for physiology or medicine for their work.
(Kristen de Groot 2021) 5

6. STRUCTURE
• Small protein containing 51 amino acids.
• Despite of 51 amino acids, insulin also have17 proteogenic amino
acids, A and B chains and 3 disulphide bridges.
• Folded with 3 alpha helices and short beta sheet segment.
• Insulin associates into dimers.
• Hexamers with stabilization of ZN2+ and phenol ligands. (Forbes
BE, 2023). 6

7. https://www.shutterstock.com/image-vector/scientific-
designing-human-insulin-structure-colorful-2104821821
7

8. FACTORS AFFECTING THE RELEASE OF
INSULIN
Glucose
Melatonin
Growth
hormone
Glucagon
like
Peptide1
Leptin
Free fatty
acids
Amino
acids
Estrogen
GH
(Fu Zhuo etal, 2014) 8

9. FUNCTIONS OF INSULIN
Tissue Effect Of Insulin
Liver Catabolic pathway
Inhibits glycogenolysis
Inhibits conversion of fatty acids and amino acids into keto acids
Inhibit the conversion of amino acids to glucose.
Anabolic pathways
Promote glucose storage as glycogen
Increase triglyceride and VLD formation
Muscle Protein Synthesis
Increase amino acid transport
Increase ribosomal protein synthesis
Glycogen Synthesis 9

10. Adipose
Tissue
Triglyceride Storage
• Lipoprotein lipase induced by insulin to hydrolyze
triglyceride in circulating lipoprotein for delivery of
fatty acids to adipocytes.
• Glucose transport in cell provide glycerol phosphate
to permit esterification of fatty acids.
• Intracellular lipase is inhibited by insulin
Brain • Decreased appetite
• Increase energy expenditure.
10

11. (Agrawal etal, 2021). 11

12. CAUSES OF INSULIN DEFICENCY
Insulin
Resistance
Destruction of
beta cells
Genetic
mutations
(Biomaterials and Biotechnology 2019)
12

13. DISORDERS RELATED TO INSULIN
DEFICENCY
• DIABETES MELLITUS
• Diabetes mellitus is a group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion, insulin
action, or both. the chronic hyperglycemia of diabetes is associated
with long-term damage, dysfunction, and failure of various organs,
especially the eyes, kidneys, nerves, heart, and blood vessels.
13

14. CLASSIFICATION OF DIABETES
Type 1 Diabetes (beta cell destruction
usually leading to insulin deficiency)
Immune mediated
Idiopathic
Type 2 Diabetes may range from predominantly insulin
resistance with relative insulin deficiency
to a predominantly secretory defect with
insulin resistance)
Other Specific Types Genetic defects of beta cell function
Chromosome 12 HNF-1 alpha (MODY3)
Chromosome 7 glucokinase (MODY2)
Chromosome 20 HNF4-alpha (MODY1)
Mitochondrial DNA
14

15. Genetic Defects In insulin Action • Type A insulin Resistance,
Leprechaunism, Rabson Mendenhall
Syndrome, Lipoatrophic Diabetes and
Others.
Endocrinopathies • Acromegaly, Cushing Syndrome,
Glucagonoma, Hyperthyroidism,
Somatostatinoma, Aldosteronoma
Uncommon Form of immune
mediated Diabetes
Gestational Diabetes
• Stiff man syndrome, anti insulin
receptor antibodies,
(American Association of Diabetes,2009) 15

16. SYMPTOMS OF DIABETES MELLITUS
https://www.pharmacyplanet.com/blog/post/type-2-diabetes-symptoms-
diagnosis-and-management
16

17. RANKS OF COUNTRIES IN DIABETES MELLITUS
EMILY JOSHU HEALTH REPORTER FOR DAILYMAIL.COM 2023.
17

18. OVERSECRETION OF INSULIN
• HYPERINSULINEMIA:
• Hyperinsulinemia (hi-pur-in-suh-lih-nee-me-uh) means the amount of
insulin in the blood is higher than what's considered healthy.
• On its own, hyperinsulinemia isn't diabetes. but hyperinsulinemia
often is associated with type 2 diabetes.
https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/expert-
answers/hyperinsulinemia/faq-20058488#:~:text
18

19. CAUSES OF HYPERINSULINEMIA
Insulin Resistance
Tumor on beta
cells
Bypass Surgery
Race, Sex ,age
Hyperinsulinemia
in newborn
(Elizabeth Woolley, 2023)
19

20. RISK FACTORS OF HYPERINSULIEMIA
▪ Obesity
▪ Sedentary lifestyle
▪ Smoking
▪ Age 45+
▪ A parent or sibling with
diabetes
▪ Heart Diseases
▪ High Blood Pressure
▪ High Cholesterol
▪ History of Stroke
▪ Sleep apnea
Symptoms of
Hyperinsulinemia
▪ Increased cravings for
sugar and carbohydrates
▪ Fatigue
▪ Difficulty losing weight
▪ Frequent hunger or extreme
hunger
(Elizabeth Woolley, 2023)
20

21. NEW RESERCHES RELTED TO INSULIN
• Topical insulin improves wound healing by regulating oxidative and
inflammatory responses.
• Insulin treatment decreases the levels of reactive oxygen species,
which can induce deleterious effects on lipids, proteins, and DNA in
burn wounds in rats.
• Topical insulin induces early recruitment of neutrophils and exerts
anti–inflammatory effect in wounds by increasing the number of m2
macrophages and il-10 levels to eliminate dead tissues.
(Wang J., X J., 2020)
21

22. • In vitro, insulin facilitates chemotaxis and phagocytosis of macrophages,
as well as secretion of inflammatory mediators by regulating mcp-1
expression at wound sites.
• In addition to regulating re-epithelialization and inflammatory responses at
wound tissues, insulin also exerts angiogenic effect on wounds. topical
insulin increases the number of newly formed blood vessels in healing
tissue.
• Subcutaneous injection of insulin stimulates microvascular endothelial cell
migration and endothelial tube formation. these biological effects are
associated with P13K-AKt-srebp1 signaling.
(Wang J., X J., 2020)
22

23. DEOSSIFICATION DUE TO INSULIN
DEFICIENCY
• Insulin is that it promotes bone development. bone formation may be
regulated by insulin signalling through osteoblast development and
bone resorption by osteoclasts.
• In vitro study, it has been reported that insulin is an anabolic agent
capable of increasing the rate of osteoblast proliferation,
• Collagen synthesis, and alkaline phosphatase production
• And it facilitates glucose uptake and subsequently inhibits the
activities of osteoclast.
23

24. EFFECT OF INSULIN ON BRAIN
• Insulin action is critically important in the developing nervous
system, directing differentiation, proliferation, and neurite growth.
• Insulin acts via its receptor to stimulate brain growth, as noted by
increased expression and activity in developing brain tissues.
• Insulin also acts as a neuroprotector, preventing damage induced by
ischemia, β-amyloid toxicity, oxidative stress, and apoptosis. thus,
brain insulin action may play a role in preventing the development of
dementia. (Agrawal etal, 2021).
24

25. https://www.researchgate.net/figure/Fig-1-Roles-of-brain-insulin-
deficiency-and-brain-insulin-resistance-in-Tau_fig1_221827935
25

26. INSULIN UPTAKE METHODS IN MODREN
WORLD
• vial and syringe
• insulin pen
• continuous subcutaneous insulin infusion
• sensor-augmented pump therapy
• inhaled insulin
• oral insulin
• colonic insulin delivery
(Investig, 2016)
• Intra peritoneal
• Ocular Route
• Rectal route
• Intra tracheal
• nasal insulin
• buccal insulin
• transdermal
26

27. INSULIN TESTS
• C-peptide is a substance that is created when the hormone insulin
is produced and released into the body. the insulin c-peptide test
measures the amount of this product in the blood.
• The normal physiological c-peptide plasma concentration in a
fasted state is 0.9 to 1.8 ng/ml.
• A high level could indicate insulin resistance, insulinoma, or
kidney disease.
• A low c-peptide is usually present in patients with type 1, or
sometimes, type 2 diabetes. (Venugopal etal, 2023)
27

28. https://labpedia.net/c-peptide-insulin-proinsulin-and-interpretations/
28

29. REFERENCES
• Forbes, B. E. (2023). The Three-dimensional Structure Of Insulin And Its
Receptor. Vitamins And Hormones, 123, 151-185.
• Senthil K. Venugopal; Myles L. Mowery; Ishwarlal Jialal. (2023). Biochemistry
Of C Peptide.
• Rahul Agrawal, Candace M. Reno, Sunny Sharma,camille Christensen,yiqing
Huang, And Simon J. Fishe (2021). Insulin Action In The Brain Regulates Both
Central And Peripheral Functions
• Ostergaard, M., Mishra, N. K., & Jensen, K. J. (2020). The ABC Of Insulin: The
Organic Chemistry Of A Small Protein. Chemistry–a European Journal, 26(38),
8341-8357.
29

30. • Zhuo Fu, Elizabeth R. Gilbert, & Dongmin Liu (2014).” Regulation Of Insulin
Synthesis And Secretion And Pancreatic Beta-cell Dysfunction In Diabetes.
• Mann, Elizabeth, Sunni, Muna, And Bellin, Melena D. (2020). Secretion Of
Insulin In Response To Diet And Hormones.
Pancreapedia: Exocrine Pancreas Knowledge Base,doi: 10.3998/Panc.2020.16
• American Diabetes Association(2009).Diagnosis And Classification Of Diabetes
Mellitus.
Jiao Wang1 And Jixiong XU (2020) Effects Of Topical Insulin On Wound Healing:
A Review Of Animal And Human Evidences 13: 719–727.
30

31. 31