The expression of mesangial alphaSMA may play a role in the progression of glomerular damage, while, on the other hand, newly acquired mesangial vimentin seems to be attenuated by heavy proteinuria. In addition, it was suggested that peritubular alphaSMA-positive myofibroblastic cells, in collaboration with interstitial macrophages, contribute to the progression of interstitial fibrosis in diabetic nephropathy.

In order to clarify the mechanism of impaired thyroid hormone levels in patients with diabetes mellitus, thyroid hormone, thyroid hormone binding inhibitor (THBI), inhibitor of extrathyroidal conversion of T4 to T3 (IEC) and free fatty acid (FFA) were examined. In addition, TRH test was performed on 9 diabetic patients showing poor control of plasma glucose before and after glycemic control. Before glycemic control, fasting plasma glucose and HbA1c were significantly higher than after glycemic control (P < 0.05). T3 and the T3/T4 ratio significantly increased and rT3 significantly decreased after glycemic control (P < 0.05). THBI index and plasma FFA level significantly decreased and %T3 production (IEC) significantly increased after glycemic control (P < 0.05). The response of TSH to TRH significantly increased after glycemic control. In conclusion, (1) the presence of THBI, (2) the presence of IEC, and (3) dysfunction of the hypothalamo-hypophysial-thyroid axis are considered to be involved in abnormal thyroid function in diabetic patients.

The effect of tri-iodothyronine injection on the nuclear tri-iodothyronine receptor (putative thyroid-hormone receptor) was examined in rat liver. Nuclear receptors were extracted from isolated nuclei with 0.4 M-KCl, and their association constants (Ka) and maximal binding capacities (Cmax.) were determined by Scatchard analyses with and without correction for the endogenous hormone. The amount of endogenous tri-iodothyronine bound to non-histone protein was estimated on the basis of the specific radio-activity of [125I]tri-iodothyronine injected 2 h before the rats were killed. It was demonstrated that Cmax. of the nuclear receptors was 2.5-fold higher in severely hyperthyroid than in hypothyroid rats. However, irrespective of the thyroid status, the Ka of the receptors remained unchanged when corrected for endogenous tri-iodothyronine bound to non-histone protein. The validity of the correction was supported by experiments in vitro in which nuclear receptors were preincubated with unlabelled tri-iodothyronine. The increase in Cmax. of nuclear receptors was directly related to mitochondrial alpha-glycerophosphate dehydrogenase activity. These results suggest a hormonal modulation of the nuclear receptors which is associated with hormonal action.

Effects of des-asp1-angiotensin II (angiotensin III) on blood pressure and aldosterone secretion were examined in man. Angiotensin III was equipotent with val5-angiotensin II amide in the stimulation of aldosterone production, but had only 20% of the pressor activity of the later. These results are consistent with those previously reported by other investigators in animals.

The biological activity of high doses of des-asp1-,ileu8-angiotensin II (AIIIA) was studied in man. In 5 normal men an intravenous infusion of 600 ng/kg/min of AIIIA for 30 min caused a slight rise in blood pressure, a decrease in plasma renin activity and an increase in plasma aldosterone. This dose inhibited pressor and steroidogenic actions of angiotensin II infused into the same 5 normal men at a rate of 20 ng/kg/min for 30 min. These results are considerably different from our previous report using lower dose (200 ng/kg/min) of AIIIA and indicate that in man AIIIA has both agonist and antagonist activities on the peripheral arterioles as well as on the adrenal cortex.