Diabetes starvation

A situation like this can come about when an organism has a high intake of lipids and a low intake of carbohydrates, but there are also other possible causes, such as starvation and diabetes. Starvation conditions cause an organism to break down fats for energy, leading to the production of large amounts of acetyl-GoA by P-oxidation. The amount of acetyl-CoA is excessive by comparison with the amount of oxaloacetate available to react with it. In the case of people with diabetes, the cause of the imbalance is not inadequate intake of carbohydrates but rather the inability to metabolize them. 

A knowledge of normal metabohsm is essential for an understanding of abnormalities underlying disease. Normal metabolism includes adaptation to periods of starvation, exercise, pregnancy, and lactation. Abnormal metabolism may result from nutritional deficiency, enzyme deficiency, abnormal secretion of hormones, or the actions of drugs and toxins. An important example of a metabolic disease is diabetes mellitus. 

Both dehydrogenases of the pentose phosphate pathway can be classified as adaptive enzymes, since they increase in activity in the well-fed animal and when insulin is given to a diabetic animal. Activity is low in diabetes or starvation. Malic enzyme and ATP-citrate lyase behave similarly, indicating that these two enzymes are involved in lipogenesis rather than gluconeogenesis (Chapter 21). 

Increased fatty acid oxidation is a characteristic of starvation and of diabetes meUims, leading to ketone body production by the Ever (ketosis). Ketone bodies are acidic and when produced in excess over long periods, as in diabetes, cause ketoacidosis, which is ultimately fatal. Because gluconeogenesis is dependent upon fatty acid oxidation, any impairment in fatty acid oxidation leads to hypoglycemia. This occurs in various states of carnitine deficiency or deficiency of essential enzymes in fatty acid oxidation, eg, carnitine palmitoyltransferase, or inhibition of fatty acid oxidation by poisons, eg, hypoglycin. 

The basic form of ketosis occurs in starvation and involves depletion of available carbohydrate coupled with mobihzation of free fatty acids. This general pattern of metabohsm is exaggerated to produce the pathologic states found in diabetes meUitus, twin lamb disease, and ketosis in lactating catde. Nonpathologic forms of ketosis are found under conditions of high-fat... 

Ketosis is mild in starvation but severe in diabetes meUitus and ruminant ketosis. 

Ketosis, a metabohc adaptation to starvation, is exacerbated in pathologic conditions such as diabetes mellitus and ruminant ketosis. 

Diabetes results from a lack of insulin secretion by the pancreas. Without insulin, cells take up glucose very slowly. The lack of insulin results in an inability to use blood glucose for fuel. Consequently, the body behaves as if it were starving even though food is available. The metabolic responses of the untreated insulin-dependent diabetic are essentially the metabolic responses of starvation. 

Starvation ( ] glucagon i insulin) Glycogen exhaustion Diabetes ( f glucagon [ insulin) Glycogen degradation Excitement ( ] epinephrine). Glycogen degradation... 

Starvation (f glucagon j insulin) Extensive protein degradation Diabetes ( glucagon insulin) Protein degradation Excitement ( epinephrine)-. Protein degradation... 

Ketogenesis (Figure 6.19) occurs in the liver at most times but is greatly accelerated when acetyl-CoA production from p-oxidation of fatty acids exceeds the capacity of the TCA cycle to form citrate, that is during periods of starvation or in diabetics who have... 

Patients with type 1 diabetes mellitus make no insulin. The classic symptoms of Type 1 diabetes are excessive hunger, constant thirst, and frequent urination. Prior to the availability of exogenous insulin, a diagnosis of type 1 diabetes was a death sentence. The optimal therapy was to restrict food intake, usually to a few hundred calories a day. This extended life. However, toward the end, the only question was whether death would come as a consequence of the disease or through starvation. 

During anaerobic glycolysis in the muscles and erythrocytes, glucose is converted into lactate, releasing protons in the process (see p. 338). The synthesis of the ketone bodies acetoacetic acid and 3-hydroxybutyric acid in the liver (see p. 312) also releases protons. Normally, the amounts formed are small and of little influence on the proton balance. If acids are formed in large amounts, however (e. g., during starvation or in diabetes mellitus see p. 160), they strain the buffer systems and can lead to a reduction in pH (metabolic acidoses lactacidosis or ketoacidosis). 

If the production of ketone bodies exceeds the demand for them outside the liver, there is an increase in the concentration of ketone bodies in the plasma (ketonemia) and they are also eventually excreted in the urine (ketonu-ria). Both phenomena are observed after prolonged starvation and in inadequately treated diabetes mellitus. Severe ketonuria with ketoacidosis can cause electrolyte shifts and loss of consciousness, and is therefore life-threatening (ketoacidotic coma). 

Addition of ethyl acetate to a specimen having a transaminase activity of 47 units was responsible for the following increases in enzyme activity 10 mg/100 ml, 60 units 20 mg/100 ml, 77 units 40 mg/100 ml, 107 units and 80 mg/100 ml, 150 units. Transaminase activity in these specimens determined by another method ranged from 32 to 34 units (C7). Thus, when serum from patients with ketosis is assayed for aspartate aminotransferase activity by the diazo method, false elevations of activity may be recorded due to reaction of acetoacetic acid. In Table 11 are shown some values obtained by the diazo method and by an ultraviolet NADH NAD aspartate aminotransferase technique (B12). Examination of the medical records of these patients indicated that they were either diabetics who were in ketosis or individuals who were eating very poorly and had some degree of starvation ketosis. Similar elevations have been observed in patients receiving p-aminosalicylic acid (G6). 

Oral Treatment of hypokalemia in the following conditions With or without metabolic alkalosis digitalis intoxication familial periodic paralysis diabetic acidosis diarrhea and vomiting surgical conditions accompanied by nitrogen loss, vomiting, suction drainage, diarrhea, and increased urinary excretion of potassium certain cases of uremia hyperadrenalism starvation and debilitation corticosteroid or diuretic therapy. 

In some ways, the metabolic profile of a patient with uncontrolled type 1 diabetes resembles that of the starved patient, except that in the complete absence of Insulin, the ketoacidosis of diabetes is much more severe than in fasting, and starvation is rarely associated with hyperglycemia. 

Acetonaemia is a clinical feature seen in diabetes and starvation and is thus not... 

Healthy, well-nourished individuals produce ketone bodies at a relatively low rate. When acetyl-CoA accumulates (as in starvation or untreated diabetes, for example), thiolase catalyzes the condensation of two acetyl-CoA molecules to acetoacetyl-CoA, the parent compound of the three ketone bodies The reactions of ketone body formation occur in the matrix of liver mitochondria. The six-carbon compound /3-hydroxy-/3-methylglutaryl-CoA (HMG-CoA) is also an intermediate of sterol biosynthesis, but the enzyme that forms HMG-CoA in that pathway is cytosolic. HMG-CoA lyase is present only in the mitochondrial matrix. 

Ketone Bodies Are Overproduced in Diabetes and during Starvation... 

During starvation or in uncontrolled diabetes mel-litus, when carbohydrates are either unavailable or not properly utilized, cellular proteins are used as fuel. 

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