mod 4 glucose regulation
what is the danger of high blood glucose levels? Why doesn't the body use the glucose in the blood as its needed rather than regulating it back down to a normal level?
Aside from the osmotic pressure that results from high glucose in the blood (which leads to the intense thirst and frequent urination observed in diabetics), the main long-term danger is from glycation.
A summary of insulin's effect on glucose metabolism. When insulin binds the insulin receptor
(1), it stimulates a number of processes that reduce blood glucose levels. It increases the translocation of GluT4 transporters (2), thus increasing the ability of the cell to import glucose from the blood (3). It also stimulates glycogen production (4), glycolysis (5), and fatty acid synthesis (6). Insulin also inhibits gluconeogenesis (7) to prevent formation of glucose from noncarbohydrate sources.
type 2 diabetes
(also known as adult-onset or non-insulin-dependent diabetes). These cases are characterized by insulin resistance, which is the failure of the body to respond to normal or even elevated concentrations of insulin.
how does glucagon stimulate the production of glucosed
Glucagon stimulates the production of glucose via gluconeogenesis by the liver as well as fatty acid and amino acid catabolism for energy
metformin
Metformin is a commonly prescribed antidiabetic drug to treat non-insulin dependent type 2 diabetes. It is derived from Galega officinalis (French Lilac).
A1C
The glycated form of hemoglobin is called A1C (other names are hemoglobin A1c, HbA1c), an
what does diabetes lead to because of the decreased ability to produce or sensitivity
This leads to excessively high blood glucose levels that are damaging to various organs and systems in the body.
what is a result of insulin stimulating the uptake and storage of glucose
This results in increased glycogenesis as well as fatty acid synthesis.
(hypoglycemia)
dangers of low blood glucose levels (hypoglycemia) are straightforward: cells in the body need access to glucose to make ATP and carry out their functions and low glucose will prevent cells from having the energy they need.
Diabetes results from a
decreased ability to produce insulin or a decreased sensitivity of cells to the insulin produced by the body (type I and type II, respectively).
what is diabetes mellitus
diabetes (meaning "to run through") and mellitus ("honey") describe an obvious symptom of the disease. Diabetes results from excessively high levels of blood glucose due to a misregulation of glucose metabolism
what do the alpha cells in the islets of langerhans secrete
glucagon when blood glucose levels are low (name, which sounds like "glucose gone," suggests its function
To safeguard against increased glucose levels, insulin also slows down the formation of
glucose from other noncarbohydrate sources (gluconeogenesis).
Insulin stimulates the uptake and storage of
glucose from the blood by cells in the body. .
how does insulin affect protein synthesis and fatty acid synthesis
increases the rates of protein synthesis and fatty acid synthesis by stimulating the uptake of amino acids and fat storage molecules, respectively.
Blood glucose levels are controlled by several hormones, predominantly
insulin and glucagon.
Metformin
is one available drug that is able to lower blood glucose by affecting the electron transport chain, gluconeogenesis, and glucose transport into cells.
type 1
juvenile-onset or insulin-dependent diabetes) is an autoimmune disease in which the immune system destroys pancreatic beta cells, thus impairing insulin production. disease results from the lack of insulin, it must be treated with insulin supplementation
how does the kidneys eliminate excess glucose
kidneys eliminate excess glucose in the blood by excreting it in urine. This process requires large amounts of water, which explains the strong thirst and urge to urinate excessively associated with the disease.
where is metformin taken up by
liver cells enters the mitochondria and binds to complex I of the electron transport chain. -binding decreases the efficiency of this complex in transferring electrons from NADH to coenzyme Q10, thus decreasing the overall production of ATP -reduced ATP production, as well as other effects of the complex I inhibition, acts as a signal to the liver cells (via various pathways still under investigation) to decrease gluconeogenesis.
what can metformiin increase the risk of
on the Cori cycle that gluconeogenesis is essential for conversion of lactate back to glucose after anaerobic fermentation in muscle and red blood cells. Treatment with metformin can therefore increase the risk of elevated lactate levels in the blood, a condition known as lactic acidosis, because it lowers the blood pH.
summary of glucose regulation
picture above shows a depiction of an islet of Langerhans containing alpha cells (purple cells) and beta cells (pink cells). 1. Low blood glucose level (hypoglycemia) stimulates secretion of glucagon from alpha cells of the pancreatic islets. 2. Glucagon acts on hepatocytes (liver cells) to accelerate the conversion of glycogen into glucose (glycogenolysis) and to promote formation of glucose from lactic acid and certain amino acids (gluconeogenesis). 3. As a result, hepatocytes release glucose into the blood more rapidly, and blood glucose level rises. 4. If blood glucose continues to rise, high blood glucose level (hyperglycemia) inhibits release of glucagon (negative feedback). 5. High blood glucose (hyperglycemia) stimulates secretion of insulin by beta cells of the pancreatic islets. 6. Insulin acts on various cells in the body to accelerate facilitated diffusion of glucose into cells, to speed conversion of glucose into glycogen (glycogenesis), to increase uptake of amino acids by cells and to increase protein synthesis, to speed up synthesis of fatty acids (lipogenesis), to slow the conversion of glycogen to glucose (glycogenolysis), and to slow the formation of glucose from lactic acid and amino acids (gluconeogenesis). 7. As a result, blood glucose level falls. 8. If blood glucose level drops below normal, low blood glucose inhibits release of insulin (negative feedback) and stimulates release of glucagon.
glycation
reaction in which a covalent bond forms between a sugar molecule and a protein or lipid molecule without the aid of an enzyme addition of the sugar can affect the function of a protein by making it more stiff and inflexible.
what does glucagon doe
stimulates liver cells to break down stores of glycogen, releasing glucose into the blood. causes the breakdown of glycogen in muscle cells and the production of glucose from amino acids. increases blood sugar between meals,supplying energy to the brain and active muscles.
what happens when insulin binds to the receptors in the cell membrane
stimulates the translocation of GluT4 to the cell membrane, thereby increasing the facilitated diffusion of glucose into the cells
The percentage of A1C under normal conditions is usually less
than 5% of hemoglobin.
elevated blood sugar levels increase the rate of glycation and the formation of AGEs that contribute to disease. The most vulnerable tissues to AGE accumulation are
those whose cells have the longest lifespan, such as nervous tissue, the retina, and collagen in connective tissue and arteries. Indeed, the arterial hardening, blindness (retinopathy), and neuropathy associated with advanced stages of diabetes are the result of the accumulation of AGEs in these organs of the body.
what is the primary aim of insulin
to maintain a safe range of glucose in the blood.
There are two main types of diabetes.
type 1 type 2
where is glucagon produced
whereas glucagon is produced in the alpha cells of the pancreas
what is the purpose of the islets of langerhans
Embedded within the pancreas which secrete hormones directly into the blood. The islets include alpha and beta cells.
what cells secrete insulin
beta cells of the pancreatic islets -opposes glucagon
Protein glycation and formation of AGEs.
Glucose will form a covalent bond with proteins and create a glycated protein. Over time, and especially when blood glucose levels are elevated, the glycated proteins will continue to react with sugars and other glycated proteins to form advanced glycation end products (AGEs). Glycation will occur at a slow, constant rate whenever proteins and sugars are in solution together.
The ability of metformin to lower blood glucose levels is attributed, in part, to two effects:
Inhibition of gluconeogenesis, thereby lowering glucose production and release by the liver. Increased translocation of GluT4 transporters to cellular membranes leading to increased glucose uptake by cells in the body, particularly muscle and fat cells.
A diagnosis of diabetes is usually made when the levels of A1C are
above 6.5%.
insulin is released in response to
and is released in response to increased blood glucose levels,
where is glucogon released in response to
and is released in response to low blood glucose levels.
nsulin is produced in the
beta cells of the pancreas