The present study was performed to investigate the effects of the antiallergic drug tranilast on the development of diabetic nephropathy in streptozotocin (50 mg/kg)-induced diabetic spontaneously hypertensive rats (SHR). Diabetic SHR were given standard chow or chow containing tranilast at a dose of 1400 mg/kg for 24 weeks. The effects of tranilast on urinary albumin excretion, mesangial expansion, expression of transforming growth factor-␤ (TGF-␤) and type I collagen mRNAs, number of anionic sites on the glomerular basement membrane (GBM), and urinary TGF-␤ and 8-hydroxy-2Ј-deoxyguanosine (8-OHdG) excretion were assessed. Tranilast did not affect the blood glucose concentration or blood pressure in diabetic SHR. Urinary albumin excretion rate and creatinine clearance were markedly increased in diabetic SHR. Tranilast treatment decreased albuminuria and hyperfiltration. Tranilast inhibited the diabetes-induced expansion of mesangial and tuft areas, as well as the increase in urinary TGF-␤ and 8-OHdG excretion, loss of anionic sites of GBM, and overexpression of TGF-␤ as determined immunohistochemically. The levels of TGF-␤ and type I collagen mRNA expression were increased in the renal cortex in untreated diabetic SHR at 24 weeks, as determined by real-time quantitative polymerase chain reaction. Tranilast treatment inhibited the up-regulation of TGF-␤ and type I collagen mRNA expression by 65 and 36%, respectively, in diabetic SHR. In conclusion, tranilast decreased albuminuria by suppressing glomerular hyperfiltration, mesangial expansion, and loss of the charge barrier via regulation of extracellular matrix gene expression and oxidative stress. Tranilast may be clinically useful in the treatment of diabetic nephropathy.

F i g u r e 1 . Cr a n i a l ma g n e t i c r e s o n a n c e i ma g i n g ( MRI ) d e mo n s t r a t e d a n a b s e n c e o f h i g h i n t e n s i t y o f t h e p o s t e r i o r p i t u i t a r y o n T 1 -we i g h t e d i ma g e s ( F i g 1 A) . Af t e r n o r ma l i z a t i o n o f t h e s e r u m s od i u m l e v e l a n d p l a s ma o s mo l a l i t y , h i g h i n t e n s i t y o f t h e p o s t e r i o r p i t u i t a r y o n T 1 -we i g h t e d i ma g e s wa s i mp r o v e d ( F i g 1 B ) . SHORT COMMUNICATION

References 1. Yamada K, Nonaka K: Diabetic ketoacidosis in young obese Japanese men: atypical diabetes induced by sugar-containing soft drinks (Letter). Diabetes Care 19:671, 1996 2. Tanaka K, Moriya T, Kanamori A, Yajima Y: Analysis and a long-term follow up of ketosis-onset Japanese NIDDM patients.

Abstract. We report a case showing deterioration of glycemic control during octreotide long-acting release (LAR) treatment in an acromegalic Japanese patient with type 2 diabetes mellitus. The patient did not show much improvement of insulin sensitivity (QUICKI; 0.33 before treatment, 0.35 during octreotide LAR treatment), and showed a significant reduction in early insulin secretion (insulinogenic index; 0.28 before treatment, 0.08 during octreotide LAR treatment) on 75 g oral glucose tolerance test (75gOGTT), despite decreases in GH and IGF-I levels during the course of octreotide LAR treatment. Postoperatively, both insulin sensitivity and early insulin secretion on 75gOGTT were improved (QUICKI 0.59, insulinogenic index 0.35). There are some reports that insulinogenic index is lower in most Japanese patients with type 2 diabetes mellitus and that early insulin secretions are significantly suppressed after administration of octreotide LAR. Although the influence of octreotide LAR on glucose metabolism varies among individuals, it is necessary to manage the deterioration of glucose tolerance during octreotide LAR treatment in acromegalic Japanese patients with decreased insulinogenic index. CHRONIC growth hormone (GH) excess seems to induce a reduction of insulin sensitivity and worsening of glucose intolerance [1], and approximately 20% of acromegalic patients have diabetes mellitus [2]. Both marked improvements in insulin resistance and reduction of glycosylated hemoglobin (HbA1c) were reported to accompany postoperative decreases in GH level in these patients [3]. Although octreotide, which is the therapeutic agent used in the treatment of acromegaly, gradually reduces the GH level [4], it also inhibits the secretions of insulin, glucagon and other intestinal hormones. Furthermore, octreotide delays gastrointestinal movement, which leads to a decrease in glucose absorption [5]. Thus, these effects of octreotide are known to influence glucose metabolism, and the changes in glucose tolerance in acromegalic patients receiving octreotide treatment vary with the individual. Here, we report an acromegalic patient showing deterioration of glucose tolerance during treatment with octreotide long-acting release (LAR), which was well tolerated and reduced mean 24-hour GH levels as effectively as multiple daily subcutaneous injections of octreotide [6], and glucose tolerance without octreotide improved following surgery for pituitary tumor. Case ReportA 46-year-old woman was admitted to our hospital for a work-up for diabetes mellitus in July 2004. Her father also had diabetes mellitus. On physical examination, her body mass index (BMI) was 20.7 kg/m 2 , blood pressure was 130/80 mmHg, and she showed acromegalic facies. Laboratory examinations were

A 54-year-old man with Graves' disease