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Although receptors for somatostatin are found in bone cells, the effect of somatostatin analogs on calcium metabolism is unknown. The authors studied, in a metabolic ward, the effect of octreotide (a long-acting somatostatin analog) and a placebo in two 6-day calcium balance periods in 8 children with Duchenne muscular dystrophy. As expected, octreotide (2 μg/kg, subcutaneously, every 8 hours) reduced serum growth hormone and somatomedin (IGF-1) to levels found in growth hormone deflciency. Octreotide enhanced calcium retention by 30% (96 mg daily [P < 0.04]) in 7 boys for whom complete data (diet, urine, and fecal calcium) were available. In 6 children with urinary calcium excretion (UCa) greater than 50 mg daily, octreotide markedly lowered UCa, from 114 ± 23 mg daily to 61 ± 9 mg daily (P < 0.03). Calcium retention occurred in patients with or without initial hypercalciuria, but the higher the basal UCa, the greater was the inhibition by octreotide (r = 0.79; P < 0.03). Inactive, nonambulatory patients had a more pronounced response of UCa to octreotide (P < 0.02). Octreotide caused a mild, nonsignificant reduction in fecal calcium, with no major changes in serum calcium, phosphorus, parathyroid hormone, urinary excretion of sodium and potassium, or in creatinine clearance. Based on the current observations and the presence of receptors for somatostatin in bone cells, this hormone may have, at least on a short-term basis, an anabolic effect on calcium, perhaps favoring its deposition in bone.

It has been reported that fatty acids preferentially inhibit serum-stimulated incorporation of sulfate by embryonic chick cartilage, suggesting that they may interfere with the effects of a proposed mediator (serum somatomedin) of the actions of growth hormone (GH). This was studied further in mammalian cartilage. Butyrate and octanoate at concentrations of 0.5 to 5 mM produced a concentration-dependent inhibition of both basal and serum-stimulated sulfate and thymidine incorporation by costal cartilage from hypophysectomized rats. Butyrate also inhibited basal and serum-stimulated sulfate incorporation in cartilage from normal pigs and normal sucklings rats. In all 3 test systems, oleate (0.2--5 mM) bound to serum albumin (4 g/dl) was ineffective. There was no evidence that fatty acids preferentially inhibited the stimulation of sulfate incorporation produced by serum.

Calcium accumulates in muscles of dystrophic hamsters (DH) and patients with Duchenne muscular dystrophy. Various Ca antagonists were beneficial to the cardiomyopathy of DH, but had only minor effects on skeletal muscle. We administered a new Ca antagonist, diltiazem, 25 mg/kg/day orally to normal and dystrophic hamsters from ages 37 to 92 days. We observed a marked reduction in muscle Ca in DH treated with diltiazem: 73% in the heart, 61% in the diaphragm, and 48% in the rectus femoris. Plasma CK was significantly lower (by 37%) in treated DH, while the elevated rate of noncollagen protein synthesis in the diaphragm was not diminished. Histologically, the most important change was a reduction in Ca deposits in the heart. Diltiazem was well-tolerated by all animals and did not modify Ca content in normal hamsters. This study suggests that diltiazem may have therapeutic value in those conditions that are accompanied by excessive accumulation of Ca in tissues, such as muscular dystrophy.

In contrast to its traditional role as a catabolic agent, epinephrine added to diaphragm muscle from hypophysectomized (hypox) rats stimulated three different processes that reflect accumulation of substances in peripheral tissue: uptake of an amino acid, α-aminoisobutyric acid (AIB), uptake of a monosaccharide, 3-O-methyl-glucose, and the incorporation of leucine and tyrosine into protein. In buffer containing 1 mg/ml ascorbate to retard oxidation of catecholamines, the minimal effective concentrations were 10-7 M for AIB transport and 5 × 10-9 M for tyrosine incorporation. Norepinephrine was less potent, but it, too, stimulated AIB transport and tyrosine incorporation. One catabolic process, glycogenolysis, was also enhanced in hypox rat diaphragms, which initially responded between 10-8-10-7 M epinephrine. On the other hand, in diaphragms from intact rats, it was necessary to raise the concentration of epinephrine to 5 × 10-4 M to stimulate AIB transport, but tyrosine incorporation was never increased....

This study explored further the hypothesis that intestinal cells have two pathways for producing large triacylglycerol-rich lipoprotein particles. The hydrophobic surfactant Pluronic L-81 (L-81) inhibits formation of chylomicrons (containing triacylglycerol synthesized from dietary fatty acids and monoacylglycerol, through the monoacylglycerol pathway), but not formation of very-low-density lipoproteins. L-81 does not inhibit lymphatic lipid transport during infusion of egg phosphatidylcholine, whose fatty acid is processed through the α-glycerol phosphate pathway and is transported in lymph in very-low-density lipoproteins. Thus, the first part of this study tested whether L-81 cannot inhibit the α-glycerol phosphate pathway, and thus L-81 can only affect chylomicron lipid secretion. Intestinal lymph fistula rats were infused with a lipid emulsion containing [1- 14 C]oleic acid, but no monoacylglycerol, to ensure that the oleic acid will be channeled to the α-glycerol phosphate pathway. Experimental rats received 1 mg/h of L-81 in their emulsion whereas control rats lacked L-81. Lymphatic triacylglycerol output, measured both chemically and radioactively, was markedly suppressed in the experimental rats as compared to the controls. Thus, these data indicate that the reason why lipid transport was unaffected by L-81 when egg phosphatidylcholine was infused was not because of the pathway used for the resynthesis of triacylglycerol from phosphatidylcholine. In the second part of this study, we measured the appearance time for chylomicron (in control rats) and for very-low-density lipoprotein (in L-81-treated rats). The appearance time is defined as the time between placement of radioactive fatty acid into the intestinal lumen and the appearance of radioactive lipid in the central lacteal. The average appearance time for the control rats was 10.8 min, which was significantly shorter than the 16.2 min in the L-81-treated experimental rats. This difference in appearance time further supports the hypothesis that chylomicron and very-low-density lipoprotein are packaged separately in the enterocytes and only the formation of chylomicron is inhibited by L-81.

Rats were administered streptozocin (STZ; 50 or 75 mg/kg i.v., tail vein) or vehicle. Approximately 2 wk later, venous and arterial catheters were implanted for subsequent (24 h later) vasopressin, electrolyte, and hemodynamic measurements. STZ-induced diabetic (STZ-D) rats demonstrated a dose-dependent increase in the plasma glucose concentration, plasma osmolality, and plasma vasopressin concentration. Mean arterial blood pressure (MABP) was unchanged, but heart rate was reduced. Diabetes-prone BB rats, maintained on or withdrawn from insulin treatment for 24–48 h, and diabetes-resistant rats were instrumented and studied as above. Spontaneous-diabetes–prone rats demonstrated increases in plasma glucose concentration and plasma osmolality similar to STZ-D rats but had significantly greater plasma vasopressin concentrations. The significant decrease in MABP observed in these animals probably contributed to the enhanced vasopressin response. We conclude that both osmotic and cardiovascular parameters play important roles in vasopressin secretion in diabetic rats.

We conducted a double-blind trial with the calcium antagonist, diltiazem (8 mg/kg/d), for 24 to 32 months in 22 boys with Duchenne muscular dystrophy, who were paired by functional activity and age. No adverse clinical or ECG effects of diltiazem were detected. In eight matched pairs, completing 28 months, manual muscle testing scores fell somewhat less in the diltiazem group (from 5.5 to 4.6) than in the placebo group (from 5.3 to 4.2), although the difference between groups was not significant (p = 0.06). The 95% confidence interval for the difference in slopes of regression lines obtained from trimonthly manual muscle tests on all subjects was markedly asymmetric in favor of the diltiazem group, but this difference was also not significant. There was less deterioration of functional activity of lower extremities in the diltiazem-treated group, when beginning and end values were analyzed (p = 0.03). However, the difference in slopes of regression lines obtained from trimonthly determinations was nonsignificant. Similarly, the beginning versus end comparisons of systolic and diastolic blood pressure showed a significantly (p less than 0.05) smaller elevation of blood pressure in the diltiazem-treated group, but no difference was observed when the slopes of all values were analyzed. All other clinical and laboratory variables were unaffected by diltiazem treatment. The findings in manual muscle tests and functional activity suggest a beneficial trend with chronic diltiazem treatment in DMD.

Bovine growth hormone (bGH) covalently bound to Sepharose was tested for biological activity in vitro on diaphragm muscle and adipose tissue from hypophysectomized rats. Only under special conditions did bGH—Sepharose seem to stimulate a—aminoisobutyric acid (AIB) transport, the incorporation of leucine into protein, or glucose utilization. Exposure of adipose tissue to GH—Sepharose, like exposure to free GH, also appeared to make the tissue refractory to subsequent stimulation by free bGH. It is doubtful, however, that GH produced these changes while still bound to the Sepharose, since material with GH—like activity was found in the medium after removal of the bGH—Sepharose by centrifugation. This active material appeared only when the incubation medium contained tissue or had been previously exposed to tissue. These findings are consistent with the hypothesis that the tissues release some substance which in turn releases active material, perhaps GH itself, from the GH—Sepharose complex. Endocrinology 92...