Exercise or insulin? Exercise is equivalent to insulin in controlling blood glucose in pre-diabetics and type-II diabetics to a larger extent. But, what is the mechanism? Ill understood, but true.
Modern lifestyle diminished significantly the everyday exercise, which is probably one of the major factors leading to the development of several metabolic diseases including type 2 diabetes, hypertension and atherosclerosis with its deadly consequences.
It has been noticed that exercise reduces insulin resistance and keep blood glucose under control, even for several hours after the exercise (>24hours).There are several postulations for this effect of exercise on muscles in the uptake of glucose and its metabolism.
In type-II diabetics the main problem may be insulin resistance, may not be insulin deficiency; because in many instances the blood insulin level is higher than normal.
There seem to be several actors for insulin resistance to develop;
muscle is a heterogeneous
tissue composed of 2 main distinct fiber categories, each with
slightly different metabolic capabilities. Type I, or slow twitch,
fibers are predominantly oxidative i.e.
contain more mitochondria than do type II, or fast twitch,
Type I fibers also seem to be more responsive to insulin, exhibiting greater insulin binding capacity and increased insulin receptor kinase activity and auto- phosphorylation compared with type II fibers.
Additionally, whole-body glucose uptake and muscle glucose transport are positively associated with type I fibers. Obese persons tend to exhibit fewer type I fibers and an increased percentage of type II fibers than do lean subjects.
tissue is not inert, rather is a potent endocrine organ producing
several proteins collectively called ‘adipokines’, several of
which regulate insulin sensitivity in a negative, while others in a
rate of fatty acid availability and subsequent uptake by skeletal
muscle can augment intramuscular triglyceride (IMTG) accumulation
not lead to oxidation.
other words, there occurs a mismatch between availability of Fatty
acids and its disposal (oxidation).
Aerobic exercise training decreases the amounts of these lipid intermediates and increases the lipid oxidative capacity of muscle cells. Thus, aerobic exercise training may prevent insulin resistance by correcting a mismatch between fatty acid uptake and fatty acid oxidation in skeletal muscle.
may be inherently high in insulin-resistant muscles. There are
several FA transporter proteins such as FABP and CD36; come to the
cell membrane and
FA uptake under physiological conditions (Insulin stimulation,
exercise of leptins).
Over-expression and permanent relocation to the cell membrane of these proteins has been seen in insulin-resistant people. This may be responsible for enhanced FA uptake.
of highly bio-active fatty acid intermediates or metabolites like
TGs, diacylglycerols (DGs), ceramides, and long-chain FA coenzyme A
(LC-CoA) triggers pro-inflammatory pathways like JNK and IKK/NF-kB.
This activation negatively affects the downstream effects of insulin
and the consequent insulin resistance.
Accumulation of these lipid intermediates, which is commonly seen for long-chain saturated FA species (such as palmitic, stearic, and arachidic esters) rather than for long-chain unsaturated FA species, in turn, has been linked to defects in the insulin signaling cascade.
Recent studies have shown that the accumulation of LC-CoA, DGs, ceramides, or any combination of these negatively affects the activation of the insulin signaling cascades described above. This inhibitory action then leads to a reduction in insulin-stimulated glucose uptake and disposal into the muscle, and insulin resistance develops.Activation of IKK/NF-κB and JNK are elevated in obesity and type 2 diabetes, while inactivation of these pathways protects against lipid-induced insulin resistan
- One consistent finding with obesity is the reduced capacity for lipid oxidation through lowered activity of key mitochondrial enzymes. Carnitine palmitoyl transferase is a particularly important enzyme responsible for fatty acid transport into the mitochondria. Reduced carnitine palmitoyl transferase activity has been consistently observed in obese. Diminished activity of mitochondrial NAD (NADH) oxidoreductase, an enzyme that reflects the overall activity of the respiratory chain, has also been shown to occur in obese non-diabetic and T2DM patients relative to lean subjects.
How endurance exercise may help to ease insulin resistance and control Blood Glucose:
Endurance training in particular is known to increase both mitochondrial quantity and quality in skeletal muscle.
Endurance exercise training reduces activation of the IKK/NF-κB pathway, as indicated by increased abundance of IκB-α and IκB-β, and significantly improves insulin action.
It also causes reversal in fatty acid–induced insulin resistance and is accompanied by an exercise-mediated enhancement of the lipogenic capacity of skeletal muscle, as evidenced by increased protein expression of mGPAT, DGAT1, and SCD1 and a resultant increase in the disposal of fatty acids toward IMTG synthesis. In parallel with this increase in triglyceride synthesis, there was a reduced accumulation of fatty acid metabolites within skeletal muscle.
Along with alterations in fatty acid partitioning on insulin sensitivity, a reduction in muscle glycogen concentration after exercise is known to be a key mediator of enhanced insulin sensitivity after exercise.
|A public demonstration of aerobic exercises (Photo credit: Wikipedia)|
Aerobic exercise increases glucose uptake by muscle during exercise, increases the ability of insulin to promote glucose uptake, and increases glycogen accumulation after exercise, all of which are important to blood glucose control.
Increase in the ratio of adenosine monophosphate (AMP) to adenosine triphosphate (ATP). As ATP is hydrolyzed in working muscle (ATP-ADP+inorganic phosphate), an increase in the ADP level provides a substrate for a reaction that replenishes ATP but also produces AMP. The increase in the AMP/ATP ratio appears to work through the activation of a protein called AMP- activated protein kinase (AMPK) to stimulate glucose transport.
5-Aminoimidazole-4-carboxamide ribonucleoside (AICAR), a chemical that can be taken up by cells and converted to an AMP analog, also stimulates glucose transport in the skeletal muscle of rodents and humans.
These questions were addressed by Edward Kraegen, PhD, University of New South Wales, Sydney, Australia, who measured insulin sensitivity in rats treated with the compound AICAR, an activator of AMPK. AICAR treatment increased whole-body insulin sensitivity, and this was associated with increased insulin sensitivity in the liver as well as in selected skeletal muscle subtypes (eg, white fiber quadriceps). Unlike the findings reported in exercising humans, and consistent with the known effect of AMPK, muscle malonyl-CoA content decreased. Malonyl-CoA is an inhibitor of IRS (Insulin Receptor Substrate). AICAR reverses glucose-induced inhibition of the key insulin action kinase Akt, together with improved fatty acid oxidation. Glitazones work in the similar way as AICAR.
These results at least suggest that the pharmacologic activation of AMPK could improve insulin sensitivity in the liver as well as selected skeletal muscle subtypes, and that this action might be due to enhanced intramyocellular lipid oxidation and disposal.
Insulin robustly stimulates the transport of glucose out of the bloodstream and into tissues, such as skeletal muscle, that express glucose transporter 4 (GLUT4), the insulin-regulated glucose transporter. Because of the high responsiveness of skeletal muscle to insulin and the large overall mass of skeletal muscle, most glucose that is cleared from the blood in response to insulin in humans is stored as glycogen in skeletal muscle.
When insulin-stimulated glucose transport into skeletal muscle is diminished—as it is in people with diabetes—the result is an inability to keep blood glucose concentrations within normal ranges. Thus, skeletal muscle plays a primary role in the maintenance of normal blood glucose concentrations.
Insulin induces its effects in skeletal muscle by first binding to its receptor sites on the extracellular side of the plasma membrane. This binding initiates a series of phosphorylation reactions that lead to the phosphorylation of several signaling intermediates on tyrosine residues, including the critical insulin receptor substrate proteins (such as IRS1 and IRS2). This process is followed by the activation of phosphatidylinositol 3-kinase and of other downstream intermediates, including 3-phosphoinositide-dependent protein kinase 1, atypical protein kinase C- ζ, atypical protein kinase C-λ, and protein kinase B (Akt).
In healthy insulin-sensitive skeletal muscle, the activation of these insulin-mediated signaling intermediates ultimately leads to an increase in glucose transport through the translocation of GLUT4 from intracellular vesicles to the plasma membrane and glycogen synthesis through the activation of glycogen synthatase.
With regard to the molecular mechanisms responsible for these observations, a single exercise session increases both the insulin-dependent activity and the number of GLUT-4 glucose transporters in the plasma membrane, as well as the content and activity of hexokinase II messenger RNA.
The effects of exercise training could be explained in part by the residual effect of the last session of exercise, but it could also be explained by long-term up-regulation, induced by training, of the number and function of the glucose transporters; capillary proliferation; and the number of IIa (red glycolytic) fibers, which have a higher GLUT-4 protein content and are more insulin-responsive.
In addition to insulin-mediated glucose uptake, contraction of muscle may lead to up-regulation and translocation of GLUT-4; independent of insulin.VEGF, or Vascular Endothelial Growth Factor, produces angiogenesis (capillary proliferation) in the skeletal muscle and is released in response to aerobic exercise. The researchers found that when insulin levels were controlled in these knockout mice they had a harder time regulating their blood plasma glucose levels. The researchers concluded that VEGF increases insulin sensitivity and glucose uptake in skeletal muscle.
Many authors suggest that increased muscle blood volume and capillary surface area for the delivery of insulin and glucose to skeletal muscle fibers may help regulate hyperinsulinemia. Increase in muscle mass with exercise may be another factor for utilization of glucose.
This information includes these findings: 1) the increase in sensitivity is not just to insulin but also to stimulation of glucose transport by the contraction/hypoxia pathway; 2) the increase in sensitivity is mediated by translocation of more GLUT4 to the cell surface in response to a submaximal stimulus; 3) it requires the presence of serum during the period of stimulation by contractions, hypoxia, or AICAR; 4) the increase in sensitivity does not require protein synthesis; and 5) up-regulation of lipid metabolism, leading to decreased toxic effect of fatty acid intermediates.
|Exercise/Contraction/Hypoxia (Photo credit: Wikipedia)|
Consider these general guidelines relative to your blood sugar level before starting Exercise — measured in milligrams per deciliter (mg/dL) or millimoles per liter (mmol/L).
- 100 to 250 mg/dL (5.6 to 13.9 mmol/L). You're good to go. For most people, this is a safe pre-exercise blood sugar range.
- 250 mg/dL (13.9 mmol/L) or higher. This is a caution zone. Before exercising, test your urine for ketones — substances made when your body breaks down fat for energy. Excess ketones indicate that your body doesn't have enough insulin to control your blood sugar. If you exercise when you have a high level of ketones, you risk ketoacidosis — a serious complication of diabetes that needs immediate treatment. Instead, wait to exercise until your test kit indicates a low level of ketones in your urine.
mg/dL (16.7 mmol/L) or higher.
Your blood sugar may be too high to exercise safely, putting you at
risk of ketoacidosis. Postpone your workout until your blood sugar
drops to a safe pre-exercise range.
While it is obvious that exercise controls diabetes, it is interesting to know how exercise accomplishes this. It is likely that there are many more other mechanisms not mentioned here because the medical community.