Aharon Cohen

Effect of longterm sucrose feeding on the activity of some enzymes regulating glycolysis, lipogenesis and gluconeogenesis in rat liver and adipose tissue

Abstract 4- to 6-fold increases in the activity of liver pyruvate kinase (EC 2.7.1.40), glucose-6-phosphate dehydrogenase (EC 1.1.1.49), NADP-malate dehydrogenase (EC 1.1.1.40) and acetyl-CoA carboxylase (EC 6.4.1.2), relative to liver protein concentration, were obtained in rats fed for 12 months on a 72% sucrose diet, as compared to rats kept on a standard laboratory chow. Feeding a 72% starch diet resulted in only 2- to 3-fold increases in the activities of these enzymes. The activity of liver 6-phosphogluconate dehydrogenase (EC 1.1.1.44) increased about 2-fold in the sucrose-fed rats and did not rise significantly on a starch diet. In adipose tissue, the activity of pentose shunt enzymes rose significantly only on the sucrose diet, whereas NADP-malate dehydrogenase rose 5-fold in sucrose and 2-fold in starch-fed rats. Fasting for 48 h resulted in a decrease in the activity of enzymes of glucose utilization and lipogenesis in the liver and adipose tissue, which on all diets was of s similar proportion with respect to the activity prior to fasting. The activity of most enzymes was reduced to 50–70% of the prefasting value; that of NADP-malate dehydrogenase decreased more pronouncedly. The activity of liver phosphoenolpyruvate carboxylase (EC 4.1.1 32) was slightly decreased on both starch and sucrose diets, whereas the activity of glucose-6-phosphatase (EC 3.1.3.9) was significantly increased in the sucrose-fed rats, indicating adaptation to gluconeogenesis from the fructose component. Each of the enzymes of gluconeogenesis responded to 48 h fasting with a rise in activity, the extent of which was not apparently related to the previous diet. The more extensive changes in enzyme activities on prolonged feeding of sucrose in comparison to starch are discussed with respect to the large share of the liver in the metabolism of carbohydrate intake on sucrose and to the role of the fructose component of sucrose in producing a pattern of adaptation of liver enzymes conducive to lipogenesis and glucose intolerance.

The Effects of Physical Activity on Mortality in the Jerusalem 70-Year-Olds Longitudinal Study

OBJECTIVE: To study the association between physical activity and mortality in older men and women.

Osteoporosis in the Cohen Diabetic Rat: Correlation Between Histomorphometric Changes in Bone and Microangiopathy

Osteoporosis is well documented in type I diabetes, but its occurrence is controversial in type II diabetes. Microangiopathy is a major complication of type I and type II diabetes. We studied bone and microvascular changes in the Cohen diabetic rat, a unique nonobese model of noninsulin-dependent diabetes mellitus. The aim of this study was to find whether there is a temporal correlation between the onset of these two complications. The diabetic rats were divided into three groups (A, B, and C) according to duration of diabetes (2 months, 3 months, and 7 to 8 months, respectively). Trabecular bone area was assessed by computerized image analysis and microangiopathy by means of renal function tests, histologic examination of the kidneys, and ultrastructural measurement of the width of capillary basement membranes. Bone density of the distal femur and vertebra was significantly reduced in the diabetic rats relative to the control rats in all three groups (Group A femur: 11.5 ± 1.6% versus 21.8 ± 3.0%, p < 0.02; Group A vertebra: 15.9 ± 1.6% versus 28.5 ± 2.0%, p < 0.02; Group C femur: 7.9 ± 1.1% versus 29.6 ± 3.5%, p < 0.001; Group C vertebra: 11.4 ± 0.7% versus 37.1 ± 1.9%, p < 0.002). Renal function tests were normal in the Group A diabetic rats and there was marked albuminuria in the Group C diabetic rats. Histologic changes in the kidneys were seen only in the Group C diabetic rats. Five of 15 Group C diabetic rats showed no albuminuria or histologic evidence of kidney damage. The bone density in this subgroup was reduced relative to controls to the same degree as that of the rats with renal damage. There was no evidence of capillary basement membrane thickening in the Group A diabetic rats. Our findings indicate that in the Cohen diabetic rat, osteoporosis precedes the onset of microangiopathy. Microangiopathy probably does not play an important role in the pathogenesis of osteoporosis in this animal model.

Carbohydrate Metabolism in Myocardial Infarction: Behavior of Blood Glucose and Free Fatty Acids After Glucose Loading

GT and concomitant FFA decreases have been examined in forty-three patients with myocardial infarction below fifty years of age with no history of diabetes, fasting hyperglycemia or glycosuria. The majority had an impaired GT, which was associated, in two thirds of the cases, with a prompt and long-lasting FFA decrease similar to, or exceeding, that of normal subjects. It is suggested that a state of differential effectiveness of insulin exists in a large proportion of patients with myocardial infarction, whereby normal response of adipose tissue persists while glucose utilization of nonadipose tissues is impaired. The association of selective unavailability of insulin with the development of arteriosclerosis is briefly discussed.

Cardiac Structure and Function and Dependency in the Oldest Old

OBJECTIVES: To examine the association between cardiac function and activities of daily living (ADLs) in an age‐homogenous, community‐dwelling population born in 1920 and 1921.

A correlative study on the occurrence of retinopathy and nephropathy in sucrose-fed diabetic rats

SummaryThe correlation of the occurrence of renal and retinal microangiopathy was studied in 139 genetically selected sucrose-fed diabetic rats. It was found that in 13% of the animals both retinal and renal lesions developed; in 20% only diabetic retinopathy and in 10% diffuse glomerulosclerosis alone was observed.

Is copper effect on glucose incorporation mediated by the insulin receptor in rat adipose tissue

SummaryThe insulin receptor is not the site for the stimulatory effect of copper on glucose incorporation into total lipids by adipose tissue; prewashing of adipose tissue of rats fed a stock diet in an insulin-free medium increases the glucose incorporation into total lipids in the presence of 0.1 unit insulin from 220 above control to 430% in the nondiabetic and from 154 to 230% in the streptozotocin-diabetic rat. In contrast, glucose incorporation in the presence of CuCl2 · 2H2O is unaffected by prewashing, being the same in the prewashed as in the unwashed adipose tissue. On the other hand, mild trypsin digestion of adipocytes decreases the glucose incorporation in the presence of 28.5 mU insulin, from 201 to 126% — whereas the effect of copper on glucose incorporation is the same in the trypsin-treated or untreated adipocyte. In order to obtain maximal copper effect the adipocyte has to be preconditioned by insulin; preincubation of diabetic adipose tissue first for one hour with 0.1 unit insulin, and another hour with 100 µg CuCl2 · 2H2O added to the medium, results in greater glucose incorporation (230% above control) than when incubated alone with either CuCl2 · 2H2O (125%) or insulin (154%) for two hours. In addition to its previously noted effect on thein vivo insulin release, copper increased the number of the insulin receptor sites in adipocytes.

Effect of Aureomycin in Rats with Chronic Alloxan Diabetes.

Summary 1. Aureomycin given to chronic alloxan diabetic rats caused an average gain in body weight of 19.0 ± 2.9 g during 28 days. Control chronic alloxan diabetic rats gained 9.6 ± 2.0 g during the same period. 2. During aureomycin administration the animals consumed more food and had increased glycosuria and diuresis.

The use of metal additive in reversed phase liquid chromatography: structure-retention relationships

Abstract The fact that biologically active molecules such as amino acids, nucleotides, nucleosides and their bases form complexes with metal cations is well known. A great deal of work is devoted to the elucidation of properties and structures of such complexes. To date most of the research in the field was done using spectroscopic and electrochemical methods. We wish to report here the use of liquid chromatography for investigating the properties of such complexes. The experimental system is rather simple, consisting of a reversed phase column and an aqueous mobile phase. The mobile phase contains the metal cations under study. To such a system we inject amino acids, nucleotides, nucleosides and their bases. These solutes form complexes with the cations in the mobile phase. Since the nature of the complexes is different from that of the parent compounds, their chromatographic behavior changes. The change can be related to the properties and structures of the complexes. The partition coefficients, and hence retention times, of all amino acids studied increased when the metal cations were introduced to the mobile phase. The increase in the retention is related to the stability of the complex. For example the retention time order is t R (Cu) > t R (Ni) > t R (Zn) > t R (Co), where t R (M) indicates the retention time with metal cation M in the mobile phase. The magnitude of the amino acidsmetal complex formation constant is K f (Cu) > K f (Ni) > K f (Zn) > K f (Co). Since the chromatographic system is that of reversed phase, longer retention times can indicate greater hydrophobic interactions. In the present case the greater hydrophobicity is due to partial charge neutralization of the amino acid by the metal cations. The degree of neutralization is a function of the stability of the complex. Adenine AMP Cytosine CMP logK f k′ logK f k′ logK f k′ logK f k′ No metal - 4.60 - 2.69 - 0.46 - 0.36 Mg(II) N.A. 4.1 1.97 2.44 N.A. 0.39 1.75 0.26 Ni(II) 1.47 4.87 2.84 2.57 N.A. 0.49 1.9 0.32 Cu(II) 2.68 9.39 3.18 3.48 2.0 0.46 N.A. 0.45 Ag(I) N.A. N.A. 4.26 1.16 N.A. 1.13 With nucleotides, nucleosides and their bases the situation is much more complicated. The metal cations can complex with the phosphate moiety of the nucleotides and/or with the base part of the molecule. This fact is also reflected in the retention behavior of these solutes. The following table shows typical behavior (Table I). In the table k′ is a measure of the partition coefficients and hence the retention times. Mg causes a decrease in the retention of the bases (as well as the monophosphate nucleotides) shown in the table: this metal is known to be bound to the phosphate group only. However, the extent of retention change is roughly the same for all solutes shown. Thus in the concentration range and pH used here, the effect of the Mg ion added to the mobile phase may be related to changes in the ionic strength. Similar arguments can be made when nickel ions are added to the mobile phase although the increase in the retention of adenine should be noted. The use of copper ions gives different results. Purines are known to complex Cu(II) better than pyrimidines. Indeed the retention of adenine and AMP increases significantly while that of cytosine and, to some extent CMP, does not change much. The presence of a heavy metal such as silver in the mobile phase increases the retention of all the solutes drastically. This is clear in view of the strong complexes formed by such metals. Similar results found with other solutes and metal cations will be discussed. The chromatographic data correlates well with that known about the structures and properties of biologically important complexes. Thus, chromatographic methods can aid scientists in analyzing bioinorganic complexes.