Question Bank-MBBS
Blood Glucose Homeostasis,
Biochemistry of Starvation
And Diabetes mellitus
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What is the normal blood glucose level? Describe the regulation of blood
glucose.
(5)
Explain the role of insulin in glucose homeostasis.
(4/3)
What are metabolic effects of glucagon? Name the insulin antagonists.(3)
Metabolic changes in starvation
(4)
Explain the biochemical basis: ketosis in starvation.
(3)
Explain the biochemical basis: glucosuria in diabetes mellitus.
Metabolic changes in diabetes mellitus
(4)
Explain the biochemical basis: cataract in diabetes mellitus.
(3)
Explain the biochemical basis: glucosuria in renal diabetes.
What is glycosuria? Mention the causes of different types of glycosuria. (3)
What is renal glycosuria? How do you differentiate it from diabetic
glycosuria?
(3)
What is glycosuria? Mention the causes of different types of glycosuria. (3)
Renal glycosuria.
(3)
Detection of reducing sugar in urine.
(3)
Oral Glucose tolerance test.
(4)
G.T.T
(3)
Discuss the interpretation of oral glucose tolerance test.
(4)
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Blood Glucose Homeostasis,
Biochemistry of Starvation and
Diabetes mellitus
Study material for: MBBS course
Contents
 Introduction
 Homeostasis: Maintenance of normal levels
 Fed-Fast Cycle: Absorptive and post-absorptive states
 Metabolic Fuel Molecules: Glucose, fatty acids, amino acids, ketone bodies
 Integration of Metabolism: Carbohydrate, lipid and protein
 Mechanism of Blood Glucose Homeostasis or
Regulation of Blood Glucose
 Normal blood glucose values: Fasting, postprandial
 Biomedical importance: Hypoglycemia, hyperglycemia
 Regulating factors: Neuronal, Hormones (hypoglycemic & hyperglycemic)
 Role of Insulin: Metabolic effects
 Role of Glucagon: Metabolic effects
 Biochemistry of Starvation
 Definition
 Metabolic changes
 Complications: Ketoacidosis, Fatty liver, Muscle-wasting
 Diabetes mellitus
 Definition
 Types: Type 1, Type 2, others
 Metabolic changes
 Biochemical basis of clinical manifestations: Polyuria, polyphagia,
polydypsia, glucosuria, weight loss, muscle weakness
 Biochemical basis of acute complications: Diabetic ketoacidosis,
Hyperosmolal non-ketotic coma
 Biochemical basis of chronic complications: Cataract, polyneuropathy,
retinopathy, nephropathy, myocardial infarction, stroke, gangrene, fatty liver
 Diagnosis: Plasma glucose estimation, glycosuria (glucosuria), oral Glucose
Tolerance Test (GTT)
 Monitoring: Plasma glucose estimation, Glycated Hb (HbA1c)
 Treatment
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 Introduction:
Homeostasis is an adaptive mechanism in a living organism that regulates its internal
environment and tends to maintain a stable, constant condition under wide
environmental variations. It allows an organism to function effectively in a broad
range of environmental conditions (both internal and external)1.
Fed-Fast Cycle (or Feed-Fast Cycle)
Human beings usually take their food intermittently, 2 to 4 times a day as large meals.
Therefore, they go through two alternating physiological nutritional states –
1) Fed or Absorptive State
2) Fasting or Post-absorptive State,
Constituting a fed-fast cycle.
Metabolic Fuel Molecules
They are sources of energy (produce ATP) for the cells.
Glucose and fatty acids, present in blood, are the major or principal metabolic fuel
molecules.
Other fuel molecules are amino acids (produced from proteins) and ketone bodies
(produced from fatty acids). However, ketone bodies are more important during
prolonged fasting and starvation than during normal physiological nutritional states.
Dietary glucose in excess is stored as glycogen and fatty acids as TAG. The
energy/calories of excess glucose and amino acids are stored as TAG in adipose
tissues.
Integration of metabolism
Carbohydrates, lipids and proteins are the principal foods providing essential fuel to
the body. Their metabolisms are interrelated, coordinated or integrated to ensure
provision of fuels to various tissues and have an impact on health and disease.
Metabolic changes or adaptations occur during blood glucose homeostasis, starvation
and in diabetes mellitus.
Reference: 1
Some important homeostatic mechanisms include maintenance of relatively constant
temperature, water and electrolyte balance and maintenance of concentrations of many
metabolically important biomolecules (e.g. glucose, pH, etc) in intracellular and
extracellular fluids, particularly in blood.
These mechanisms are controlled by processes known as negative feedback and
positive feed forward. In these processes, the system responds to environmental
changes by releasing molecules, such as hormones, to exert an effect on the body that
will reverse a high or low trend and restore levels to within the normal range.
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Mechanism of Blood Glucose Homeostasis or
Regulation of Blood Glucose Concentration
The blood glucose level is normally maintained within fairly narrow range. In a
healthy individual, the normal fasting blood glucose level is 70-110 mg /dl
(Normoglycemia). After ingestion of a meal (post prandial) blood glucose level may
normally rise to 120-140 mg /dl.
Maintenance of normal blood glucose level is important because Brain, RBC and renal medulla have an obligatory requirement for glucose as
energy source.
 Increased blood glucose level (Hyperglycemia) can cause complications of
Diabetes mellitus.
 Decreased blood glucose level (Hypoglycemia) can cause coma and even
death mainly due to deprivation of glucose to brain.
Homeostasis mechanisms are brought into play following a meal when the blood
glucose level rises and again during fasting, when the level falls.
Plasma glucose concentration is dependent on the quantity of glucose that enters
circulation from various sources and the amount that is utilized by tissues, as shown in
the figure below.
Sources of blood glucose
Dietary intake,
intestinal absorption
Glycogenolysis (liver)
Utilization of blood glucose
Blood
Blood
Glucose
Gluconeogenesis
Glycolysis and TCA cycle
Glycogenesis (liver)
Fatty acid synthesis
TAG synthesis
Capillary
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Factors regulating blood glucose level are as follows.
a. Neuronal Activity
b. Hormones
Neuronal Activity
Eating behavior which influences the glucose levels is controlled by hypothalamus
(satiety centre and feeding centre) in response to falling and raising blood glucose
levels.
Hormones
Insulin and Glucagon are the principal hormones for controlling plasma glucose
levels.
Insulin decreases the blood glucose level and is called hypoglycemic hormone.
Glucagon raises the blood glucose level and is called hyperglycemic hormone.
The hormones epinephrine, glucocorticoids (cortisol), growth hormone and thyroid
hormones also raise the blood glucose level and are hyperglycemic hormones. The
metabolic actions (effect) of glucagon, epinephrine, glucocorticoids (cortisol), growth
hormone and thyroid hormones are opposite to that of insulin and therefore they are
called insulin antagonists.
Hormones are the principal mediators of metabolic changes required for glucose
homeostasis. They regulate activities of1) key enzymes of metabolic pathways
(By induction/repression, phosphorylation/dephosphorylation etc)
2) membrane transporters
Important tissues involved and targeted by hormones in the maintenance of blood
glucose level are liver, adipose tissue and skeletal muscles.
During the fed state, blood glucose level tends to rise due to intestinal absorption of
glucose.
However, glucose is converted to storage compounds – glycogen in liver and
triacylglycerol in adipose tissue preventing the rise of blood glucose level.
During the fasting state, blood glucose level tends to decrease due to utilization of
glucose by cells for energy. However, this is countered by mobilization of glucose
from glycogen, synthesis of glucose (both in liver) and mobilization of alternative fuel
molecules – free fatty acids (from adipose tissue) and ketone bodies (from liver).
Amino acids (from tissue proteins – mainly skeletal muscles) and glycerol (from
adipose tissue) are utilized in the liver to synthesize glucose.
Alternative fuel molecules – free fatty acids, aminoacids and ketone bodies have
glucose-sparing effect because they are utilized by cells for energy in preference to
glucose.
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Role of Insulin in Glucose Homeostasis
Insulin is secreted by -cells of pancreas in response to raising blood glucose level
during fed state.
Insulin brings down blood glucose level (hypoglycemic in action) by increasing
utilization of glucose by cells as shown below.
Another action of insulin is that it inhibits the secretion of glucagon, which is an
insulin antagonist.
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Actions of Insulin (Metabolic effects)
Extrahepatic cells
Liver
(eg. skeletal muscle, adipose tissue)
↑ Glucose transporter
↑Glucokinase → ↑ Glucose uptake
(GLUT-4)

↑ Glucose uptake into cells
Capillaries
↑Lipoprotein Lipase

Adipose Tissue
 Hormone-Sensitive Lipase

↑ Glycogenesis
↑ Mobilization of fatty acids
 Glycogenolysis
from VLDL and chylomicrons
 Gluconeogenesis
and entry to Adipose tissue
↑ Glycolysis →↑ Acetyl CoA

↑ Fatty acid synthesis
↑TAG synthesis→ ↑VLDL export
↑TAG synthesis
 Free Fatty acid
release into blood
 Blood glucose
concentration
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Role of Glucagon in Glucose Homeostasis
Glucagon is secreted by -cells of the pancreas in response to falling blood glucose
level.
Glucagon raises blood glucose level by mechanisms shown below.
Glucagon also mobilizes fatty acids and glycerol from adipose tissue.
Fatty acids are the most important alternative fuel molecules and glycerol serves as
substrate for gluconeogenesis.
Actions of Glucagon
(Metabolic effects)
Liver
↑Glycogenolysis
Glycogenesis
↑ Gluconeogenesis
Glycolysis →  Acetyl CoA

Fatty acid synthesis

TAG synthesis
Adipose Tissue
↑Hormone Sensitive Lipase
TAG synthesis
↑ Free Fatty acid release into blood
↑Glucose- sparing action
↑ Blood glucose
concentration
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Biochemistry of Starvation
Starvation is a state caused due to acute deprivation of food for more than 18
hours.
It may result from:
– An inability to obtain food Eg: famine, natural calamities, war.
– From the desire to lose weight rapidly
Metabolic changes in Starvationare adaptations of the body to lack of fuel supply and are an exaggeration of the
normal response of the body to fasting.
The metabolic changes are required to:
provide energy to brain and other glucose-requiring tissues
provide alternative fuel molecules–Free fatty acids & ketone bodies to other
tissues
principally involve degradation of stored forms of metabolic fuel- glycogen, TAG
and proteins
The cause and effect chain of metabolic changes in starvation
Starvation (absence of food) →  Basal Metabolic Rate
Falling blood glucose level
Decrease in insulin secretion and an increase in glucagon release
( Insulin/glucagon ratio).
Changes in the metabolisms of carbohydrate, fat and proteins
(mainly in liver, adipose tissue and skeletal muscles, respectively)
↑ Mobilization of glucose from liver to blood
↑ levels of fatty acids and ketone bodies in plasma
 utilization of glucose
↑ utilization of fatty acids and ketone bodies by cells
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Complications of Starvation
Major complications of starvation are-Ketoacidosis
-Fatty liver
-Muscle-wasting
Biochemical basis (mechanism):
Falling blood glucose level
 Insulin/glucagon ratio
↑ Lipolysis (in adipose tissue)
↑ Gluconeogenesis (in liver)
↑ Plasma free fatty acids
↑ Hepatic uptake of free fatty acids
↑Triacylglycerol synthesis in liver
Fatty liver
 Oxaloacetate (in liver)
↑ catabolism
↑ Acetyl CoA (in liver)
of skeletal
muscle
protein
↑ Ketogenesis (in liver)
Ketosis - Ketoacidosis
Muscle wasting
Coma → Death
Diabetes Mellitus
Introduction:
Diabetes mellitus is a major public health problem affecting about 3% of global
population. Diabetes mellitus is the 3rd leading cause of death in many developed
countries (after heart disease and cancer). India is the ‘Diabetes Capital’ of the world.
The prevalence of diabetes mellitus in urban India is 12.1% (2001-National Survey),
is rising, and is higher in South India than in the North.
Definition: Diabetes mellitus is a metabolic disorder characterized by hyperglycemia.
Types: The most common areType 1 diabetes mellitus
[Formerly Insulin-Dependant Diabetes Mellitus or IDDM, Juvenile-onset]
o destruction of insulin producing -cells leading to absolute insulin deficiency
may be caused due to viral infection and autoimmune attack
o blood level of insulin is always very low
o comprises about 10 % of diabetic cases
o patients < 35 years age
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