Title: Pathophysiology and Complications of Diabetic Ketosis
Kinnaird College For Women University Lahore
Course: Biochemistry
Pathophysiology of Diabetic Ketosis:
Pancreas make glucose and releases it in bloodstream. Normal functions of insulin are given
below:
• Insulin helps glucose to move into the cells where it is used for energy. And body stores
extra glucose in the liver, muscles and fat cells
• Insulin increases glucose uptake by liver, skeletal muscles and adipose tissues.
• Then in liver uptake of glucose enhances gluconeogenesis (formation of glycogen). In
skeletal muscles it enhances protein synthesis. And in adipose tissues it enhances
adipogenesis (formation of adipocytes/fat cells from stem cells).
Both starvation and un-treated diabetes mellitus are the main cause of excessive production of
ketone bodies in liver. Under starvation condition, gluconeogenesis (formation of glucose from
non-hexose precursor) occurs which cause depletion of intermediates (especially oxaloacetate) of
citric acid cycle, in result it diverts acetyl-CoA towards ketone bodies production. Normally insulin
inhibits ketogenesis whereas, glucagon stimulates it. In case of un-treated diabetes, insulin level is
insufficient and glucagon level is high which lead to accelerated gluconeogenesis and
glycogenolysis in hepatic tissue, that further increases the levels of counterregulatory hormones
(cortisol, glucagon, epinephrine and nor-epinephrine) in blood. This is because extra-hepatic tis
sues (adipose and muscle tissues) do not take up glucose sufficiently from blood (to convert it
either into fat or use it as fuel) which ultimately leads to accelerated lipolysis and proteolysis
respectively. In this diseased condition, malonyl-CoA (precursor of fatty acid synthesis in liver)
levels fall due to which carnitine acyltransferase 1 become active. This activation of carnitine
acyltransferase 1, fatty acids become able to enter mitochondria so that they are degraded to acetyl-
Kinnaird College For Women University Lahore
Course: Biochemistry
Pathophysiology of Diabetic Ketosis:
Pancreas make glucose and releases it in bloodstream. Normal functions of insulin are given
below:
• Insulin helps glucose to move into the cells where it is used for energy. And body stores
extra glucose in the liver, muscles and fat cells
• Insulin increases glucose uptake by liver, skeletal muscles and adipose tissues.
• Then in liver uptake of glucose enhances gluconeogenesis (formation of glycogen). In
skeletal muscles it enhances protein synthesis. And in adipose tissues it enhances
adipogenesis (formation of adipocytes/fat cells from stem cells).
Both starvation and un-treated diabetes mellitus are the main cause of excessive production of
ketone bodies in liver. Under starvation condition, gluconeogenesis (formation of glucose from
non-hexose precursor) occurs which cause depletion of intermediates (especially oxaloacetate) of
citric acid cycle, in result it diverts acetyl-CoA towards ketone bodies production. Normally insulin
inhibits ketogenesis whereas, glucagon stimulates it. In case of un-treated diabetes, insulin level is
insufficient and glucagon level is high which lead to accelerated gluconeogenesis and
glycogenolysis in hepatic tissue, that further increases the levels of counterregulatory hormones
(cortisol, glucagon, epinephrine and nor-epinephrine) in blood. This is because extra-hepatic tis
sues (adipose and muscle tissues) do not take up glucose sufficiently from blood (to convert it
either into fat or use it as fuel) which ultimately leads to accelerated lipolysis and proteolysis
respectively. In this diseased condition, malonyl-CoA (precursor of fatty acid synthesis in liver)
levels fall due to which carnitine acyltransferase 1 become active. This activation of carnitine
acyltransferase 1, fatty acids become able to enter mitochondria so that they are degraded to acetyl-
