Insulin, Glucagon, and
Diabetes Mellitus
By:
Insulin Effect on Carbohydrates
metabolism
Promotes muscle glucose uptake and
metabolism
Generally muscles are slightly permeable to glucose in resting state, except during
moderate/ heavy exercise, and a few hours after a meal when the liver
produces insulin.
Storage of glycogen in muscle
Glucose entering muscle cells( in resting condition) is stored as muscle glycogen,
which later support extreme energy use and provides spurts of anaerobic
energy leading o lactic acid accumulation.
Insulin action on liver
1. inactivates liver phosphorylase (enzyme causing
liver glycogen to split into glucose)
2.increases the activity of the enzyme
glucokinase (enzyme causing initial phosphorylation of
glucose after it diffuses into the liver cell)
Increases the activity of the glycogen synthase
How glucose is released between
meals?
when blood glucose level is low
• Pancreas decreases insulin secretion
• Lack of insulin stops the action of glycogen synthase
(preventing further uptake of glucose by liver from
blood)
• Lack of insulin also activates the enzyme
phosphorylase (enzyme splitting glycogen to glucose
phosphate)
• Lack of insulin activates glucose phosphatase
(splitting glucose phosphate to glucose which can
leave the cell)
Insulin Effect on other cells
1. The Brain
the brain cells are permeable to glucose and can use glucose
without the intermediation of insulin.
Unlike other cells brain cells doesn’t use any other source of
energy but glucose. When the blood glucose falls too low, into
the range of 20 to 50 mg/100 ml, symptoms of hypoglycemic shock
develop, characterized by progressive nervous irritability that
leads to fainting, seizures, and even coma.
2. Adipose Tissue
insulin promotes deposition of fat in these cells
Effect of insulin of fat metabolism
the long-term effect of
insulin lack in causing
extreme
atherosclerosis, often
leading to heart
attacks, cerebral
strokes, and other
vascular accidents
Insulin Promotes Fat Synthesis and
Storage
insulin increases the utilization of glucose by most of
the body's tissues this will decrease the utilization of
fat.
insulin also promotes fatty acid synthesis. This is when
more carbohydrates are ingested than can be used for
immediate energy, providing the substrate for fat
synthesis.
Almost all this synthesis occurs in the liver cells, and the
fatty acids are then transported from the liver by the
blood lipoproteins to the adipose cells to be stored.
Role of Insulin in Storage of Fat in the
Adipose Cells
Insulin inhibits the action of hormone-sensitive lipase.
(enzyme that causes hydrolysis of the triglycerides already
stored in the fat cells)
Insulin promotes glucose transport through the cell
membrane into the fat cells
Therefore, when insulin is not available, even storage of
the large amounts of fatty acids transported from the
liver in the lipoproteins is almost blocked.
Insulin Deficiency
Effect of Insulin on Protein
Metabolism and on Growth
Insulin is required to promote protein Synthesis and Storage.
1. Insulin stimulates transport of many of the amino acids into the
cells. (especially valine, leucine, isoleucine, tyrosine, and
phenylalanine). insulin shares with growth hormone the capability
of increasing the uptake of amino acids into cells, but the amino
acids affected are not necessarily the same ones!
2. insulin operates an "on-off" mechanism, of messenger RNA
translation, leading to formation of new proteins.
3. Insulin inhibits the catabolism of proteins→ decrease the normal
degradation of proteins →less amino acids released from cells.
4. insulin depresses the rate of gluconeogenesis → suppression of
gluconeogenesis conserves the amino acids in the protein stores
of the body.
In insulin deficiency vice versa occurs
Insulin and Growth Hormone Interact
Synergistically to Promote Growth
Factors effecting Insulin secretion
insulin secretion by the pancreatic beta cells in
response to increased blood glucose concentration,
the primary controller of insulin secretion
Other nutrients, such as certain amino acids, can also
stimulate insulin secretion.
Some hormones, such as glucagon and gastric
inhibitory peptide, as well as acetylcholine enhance the
effect of glucose, although they do not have major
effects on insulin secretion in the absence of glucose.
Other hormones, including somatostatin and
norepinephrine (by activating -adrenergic receptors),
inhibit exocytosis of insulin.
Insulin secretion levels
At normal fasting blood sugar (80-90mg/100ml) the rate of insulin
secretion is minimal 25ng/min/kg of body weight.
When blood glucose level increases, insulin secretion increases in
2 stages:
Plasma insulin concentration increases almost 10-fold within 3 to 5
minutes after the acute elevation of the blood glucose; this
results from immediate dumping of preformed insulin from the
beta cells of the islets of Langerhans. The insulin concentration
decreases about halfway back toward normal in another 5 to 10
minutes.
Beginning at about 15 minutes, insulin secretion rises a second
time and reaches a new plateau in 2 to 3 hours, this time usually at
a rate of secretion even greater than that in the initial phase. This
secretion results both from additional release of preformed
insulin and from activation of the enzyme system that synthesizes
and releases new insulin from the cells
Glucagon Effects on Glucose
Metabolism
promote breakdown of liver glycogen (glycogenolysis) and
increase gluconeogenesis (using up amino acids) in the liver.
→greatly enhancing the availability of glucose to the other
organs of the body.
in very high concentrations it also
(1) enhances the strength of the heart
(2) increases blood flow in some tissues, especially the kidneys
(3) enhances bile secretion
(4) inhibits gastric acid secretion.
(5) activates adipose cell lipase and inhibits the storage of
triglycerides in the liver, making additional amounts of fatty
acids available for the other tissues of the body.
All these effects are probably of minimal importance in the
normal function of the body.
Factors stimulating Glucagon
secretion
Amino acids stimulate
the secretion of
glucagon in the same
way it stimulates insulin
secretion (↑amino acid→
↑glucagon).
Exhaustive exercise also
stimulates glucagon
secretion for not
understood reasons.
Somatostatin effect
Factors stimulating its secretion
1. increased blood glucose
2. increased amino acids
3. increased fatty acids
4. increased concentrations of several of the gastrointestinal hormones
released from the upper gastrointestinal tract in response to food
intake.
In turn, somatostatin has multiple inhibitory effects as follows:
1. depress the secretion of both insulin and glucagon.
2. decreases the motility of the stomach, duodenum, and gallbladder.
3. decreases both secretion and absorption in the gastrointestinal tract
As a result, it decreases the utilization of the absorbed nutrients by
the tissues, which preventing rapid exhaustion of the food and
therefore making it available over a longer period of time .
Diabetes mellitus
a syndrome of impaired carbohydrate, fat, and protein
metabolism caused by either lack of insulin secretion or
decreased sensitivity of the tissues to insulin.
Type I diabetes, also called insulin-dependent diabetes
mellitus (IDDM), is caused by lack of insulin secretion.
Type II diabetes, also called non-insulin-dependent diabetes
mellitus (NIDDM), is caused by decreased sensitivity of
target tissues to the metabolic effect of insulin. This
reduced sensitivity to insulin is often called insulin
resistance.
