This document summarizes diabetes mellitus and the gluconeogenesis process. It discusses that diabetes is a metabolic disorder where the body cannot properly use or produce insulin, resulting in high blood glucose. The two main types of diabetes are described. Gluconeogenesis is introduced as the process where glucose is synthesized from non-carbohydrate sources like amino acids, particularly in diabetes where insulin is insufficient or cells are resistant to it. Key enzymes and regulatory steps in gluconeogenesis are outlined, noting its importance in providing glucose during periods of biological starvation in diabetes.

1. DIABETES MELLITUS
&
GLUCONEOGENESIS PROCESS
MADHURIMA ROY
M.Sc. (AN); 1ST YEAR
NIN (ICMR); HYDERABAD

2. Diabetes mellitus a chronic metabolic disorder that
prevents the body to utilize glucose completely or partially.
It is characterized by raised glucose concentration in the
blood.
Diabetes mellitus are mainly two types.
Type 1: insulin dependent. Due to lack of insulin secretion.
Type 2: non insulin dependent. Due to insulin resistance of
target tissue.
.

3. Blood glucose is mainly regulated by some hormones like
insulin, glucagon, glucocorticoids, epinephrine & norepinephrine,
growth hormone etc.
These hormones also control the carbohydrate metabolism by
regulate the enzymes which are participated in carbohydrate
metabolism.

4. Insulin glycogenesis
Glucagon glycogenolysis, gluconeogenesis, glycolysis
etc.

5. In case of diabetes mellitus the plasma glucose level is ↑↑ but
the cellular glucose uptake process is ↓↓- the body faces a typical
condition called biological starvation.
In this condition the glucagon level and other hormone like
epinephrine, nor epinephrine, glucocorticoids etc. are elevated,
and triggers the gluconeogenesis process.

6. Gluconeogenesis occurs in diabetes mellitus because-
1) Elevated level of glucagon
2) Insufficiency/inactivity of insulin.
3) Biological starvation condition
4) Large amount of amino acid in blood- lacking of insulin increases the
release of amino acid from muscles & extra hepatic tissue.

7. GLUCONEOGENESIS
The process of synthesis glucose from non-
carbohydrate source.
The major substrates of gluconeogenesis :
are the glucogenic amino acids and lactate, glycerol,
and propionate, acetyl-coA etc.
FEATURES OF GLUCONEOGENESIS:
SITE: liver & kidney
COMPARTMENT: cytoplasm (mitochondria also participate)
NATURE: anabolic

8. Gluconeogenesis is the reversal of glycolysis ……. Its
not true
Though both the pathways share several steps; 7 of the 10
enzymetic reactions of gluconeogenesis are the reverse of
glycolytic reaction but three reactions are not.
These three reaction of glycolysis are essentially irreversible.
In gluconeogenesis these steps are bypassed by a separate set
of enzymes.

9. glucose
Glucose-6-phosphate
Fructose-6-phosphate
fructose 1,6-bisphosphate
G-3-P + DHAP
1,3-bisphospho glycerate
3-phosphoglycerate
2-phosphoglycerate
Phosphoenol pyruvate
pyruvateoxaloaceate
phosphohexoisomerase
aldolase
G-3-P dehydrogenase
Phosphoglycerate kinase
Phosphoglycerate mutase
Enolase
Hexokinase
PFK-1
Pyruvate kinase
Pyruvate carboxylase
Fructose 1,6-bisphosphatase
Glucose-6-phosphatase

10. 1st step of gluconeogenesis
Glucagon and epinephrine increases the activity of
PYRUVATE CARBOXYLASE.
Acetyl coA is a positive allosteric modulator of PYRUVATE
CARBOXYLASE.
Glucagon turning on the genes which are coding for PEP
CABOXYKINASE.

11. 2ND REGULATORY STEP OF GLUCONEOGENESIS
Fructose2,6-bisphosphate is a negative allosteric effector for
the enzyme FRUCTOSE1,6-BISPHOSPHATASE
Fructose1,6-bisphosphatase

12. When F2,6BP conc. Is high ↑↑ the PFK-1 activity and when
conc. Becomes low ↑↑ FBPase-1 activity.
The cellular level of F2,6BP regulated by insulin and glucagon.

14. 3rd regulatory step of gluconeogenesis:
Glucagon turning on the genes which are coding for Glucose
6-phosphatase.

15. Protein modification in diabetes mellitus:
Protein can be converted in glucose by a process called
gluconeogenesis (new production of glucose). However, the rate of
protein conversion to glucose in people with diabetes depends on
the amount of insulin available and the degree of blood glucose
control
In persons with poorly controlled diabetes, this conversion can
occur rapidly and affect blood glucose control negatively
Name of the glucogenic amino acids:
Glycine, Serine ,Valine, Histidine, Arginine, Cysteine, Proline,
Alanine, Glutamate, Glutamine, Aspartate, Asparagine, Methionine.

16. Protein degradation and conversion of both endogenous and
exogenous protein to glucose in type 1 diabetes depends on the state
of insulinization and degree of glycemic control. In insulin-deficient
individuals, both limited and excess dietary protein can have adverse
effects. Conversion of excess dietary or endogenous protein to
glucose may adversely influence glycemic regulation.
In people with controlled type 2 diabetes, protein intake does not
increase blood glucose levels. However, in individuals who still produce
insulin, protein intake is just as potent as glucose in stimulating insulin
release

17. References
•Lehninger Principles of Biochemistry; 6th Edition
David L. Nelson and Michael M. Cox; W. H. Freeman & Company
•Biochemistry, 5th edition
Jeremy M Berg, John L Tymoczko, and Lubert Stryer.
New York: W H Freeman; 2002.ISBN-10: 0-7167-3051-0
• Harper's Illustrated Biochemistry, 28th Edition
Robert K. Murray, Victor W. Rodwell, David Bender, Botham, P. Anthony Weil, Peter
J. Kennelly
McGraw Hill Professional, 02-Jun-2009
•Krause's Food & Nutrition Therapy / Edition 12
by Janice L Raymond, Sylvia Escott-Stump
ISBN:1416034013;ISBN-13:9781416034018; Edition:12
Pub. Date:September 2007; Publisher:Elsevier Health Science
•peopleanddiabetes.com/id49.html
•Marion J. Franz, MS, RD, LD, CDE
Protein Controversies in Diabetes
Diabetes Spectrum
Volume 13 Number 3, 2000, Page 132

18. Thank you