Discussion

Data of the present study showed that the levels of glucose in diabetic untreated rats were steadily increased with the progress of time and then decreased but still higher than that of the control or diabetic treated rats (Table 1). Debnam and Ebrahim (1989) reported that insulin stimulation of glucose uptake (in vivo) in diabetic intestine involves events at the brush border membrane. The mechanisms include an increased surface area for uptake and enhanced transmembrane electrical gradient. The later will have a major effect on the transport of other substances when the uptake pathway is primarily Na⁺ dependent. In vitro, insulin was found to stimulate glucose uptake. The enhancement at the brush border is involved and the mechanisms include an increased surface area for uptake and an electrical gradient. This conclusion agrees well with that of previous study (Hopfer, 2000) which suggested that changes in the Na⁺ conductance of the brush boarder membrane may result in an increase in the electrochemical gradient g Na⁺ across the brush border membrane in diabetic rats (Debnam et al., 1988).

Also, the obtained data revealed that the glycogen disturbances in diabetic untreated rats were higher than that of control or diabetic treated rats. Chatila and West (1996) reported that during periods of hyper- glycemia glucose freely enters the hepatocytes driving glycogen synthesis, which was augmented further by adminstration of insulin to supra- physiological levels.

The accumulation of excessive amount of glycogen in the liver of diabetic untreated rats might be a function of intermittent episodes of hyperglycemia and hypoglycemia. The authers added such abnormalities are readly reversible with sustained euglycemic control and this is a state of insulin resistant rather than glycemic control.

In diabetic untreated rats serum and hepatic copper contents were significantly elevated in comparison with control or diabetic treated rats. Kryska and Kiczka (2002) reported that in hepatic disorders, the serum copper concentration is usually elevated. This may be caused either by necrosis of hepatocytes or disturbances in hepatic clearance. The deficiency of ceruloplasmin or its structural changes may also affect copper binding, moreover, Miniuk et al., (1989) mentioned that liver is the most important organ for copper homeostasis. At least 3 processes (played a decisive role for regular copper metabolism) take place in the preparation of copper elimination with bile, temporary storage of copper and incorporation of copper into ceruloplasmin. So, the increased copper conc. in both serum and hepatic tissue in diabetic untreated rats may be attributed to the imbalance between copper elimination, storage or incorporation that was associated with uncontrolled diabetes. Absence of such alterations in diabetic treated or control rats may augment such suggestion. 

Magnesium contents of plasma and liver were significantly decreased allover diabetic stages. A poor intracellular magnesium concentration may result in defective tyrosine – kinase activity at the insulin receptor level and exaggerated intracellular calcium concentration. Both events are responsible for the impairment in insulin action and a worsening of insulin resistance in non- insulin dependent diabetic patients (Paolisso and Barbagalls, 1997). Moreover, in Mg⁺ deficiency, extracellular magnesium concentration is drastically reduced. Membrane permeability and turnover of Na⁺, K⁺ and Ca²⁺ may be increased. Upon the increase of intracellular Ca²⁺ passive K⁺ efflux is enhanced (Gunther 1986).

In the present study, plasma calcium levels were decreased in all periods investigation in diabetic untreated rats as compared to those of normal rats. The regulation of the concentration of cytosolic free calcium under conditions of limited ATP availability is of critical importance for cell survival (Brecht and Groot, 2003). The elevated levels of calcium activate a number of hydrolytic enzymes such phospholipase A₂  which in turn damage the cell membrane and associated structures (Sakaida et al., 1992). In contrast, current results indicated a significant increase in hepatic tissues allover the experimental periods in diabetic untreated rats as compared to those of diabetic treated or control rats. It has been previously reported that calcium elevation in hepatocytes was associated with constriction of pericanalicular microfilaments which might play a role in stimulating bile secretion (Watanabe & Philips, 1984). Moreover, calcium metabolism was reported to be altered in diabetic patients as a sequence to increased Ca²⁺ excretion in the urine, decreased Ca²⁺  absorption in the intestine and reduced bone mass (Gallagher and  Lambett, 1982). 

The plasma Na⁺ content was significantly decreased in diabetic untreated rats at 15 days of the experiment in comparison with those of diabetic treated or control rats, then a non- significant steadily increase in its level was observed allover the other experimental periods. O’Hare et al., (1985) reported that a significant increase of total exchangeable Na⁺ in diabetic patients was associated. The  increased filtered load of glucose in diabetes patients was associated. The increased filtered load of glucose in diabetes will, via activation of the sodium /glucose co- transported, stimulates proximal tubular Na⁺, K⁺ Atpase activity and increased tubular sodium reabsorption (Korner et al., 1994). The glomerular lesions and hypertension may be related to the sodium retention induced by hyperglycoemia. In contrast to the plasma, the liver tissue content of sodium was increased then decreased again as compared with those of diabetic treated and control rats. Filed and Hirosa, (1966) attributed such changes to glucose – induced osmotic diuresis. Initially these are losses of water, Na⁺ and chloride from the extracellular fluid but in continuation, loss also occurs from the intracellular component. Debnam et al. (1988) attributed the flactuation in plasma Na⁺ contents to the increased transport mediated via an altered electrochemical gradient for Co- Transport of Na⁺ across the brush border membrane.

Plasma content of K⁺ was significantly decreased in diabetic untreated rats in comparison with diabetic treated and control rats. It is well established that stimulatory glucose concentrations induce a decrease in K⁺ conductance because of the closure of K- Atpase channels. Moreover, liver K⁺ contents were significantly increased at 15 days then slightly decreased during the other experimental periods. Haddad et al., (1991) reported that the swelling of hepatocytes induced by hypotonic media is associated with an increase in K⁺ conductance, consistent with opening of K⁺ channels. The ensuring efflux of electrolytes and water through these channels is thought to decrease hepatocellular volume toward basol values (Lidofsky and Roman, 1997).

The results suggest that the endocrine imbalance associated with  diabetes was responsible for the alterations of transport and metabolism of the studied ions. Also the results point out the possibility that alterations in plasma & tissue levels of those ions contribute to the development of liver complications associated with long – term diabetes. Insulin treatment was also able to correct the ionic imbalance occured in diabetes.

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Table 1: Plasma glucose and ions concentrations in control and diabetic rats.

- Values represent means ± SE, n = 10

- The two means in the same raw having a difference equal to or more than the corresponding LSD value are significantly

  Different from each other at P< 0.05

Table 2: Glycogen and ions contents of liver tissue in control and diabetic rats.

-Values are means ± SE. , n= 5

-The two means in the same raw having a difference equal to or more than the corresponding LSD value are significantly different from other    at P<0.05.