Trypsin-treatment of isolated rat adipocytes abolishes the metabolic effects not only of insulin, but also of the insulin-like growth factors : in trypsin-treated cells, concentrations of these hormones that are otherwise maximally effective no longer stimulate 3-0-methylglucose transport and lipogenesis or inhibit epinephrineinduced lipolysis. Concomitantly, the trypsin-treated adipocytes no longer display specific insulin binding. In contrast, the characteristics of the binding of the insulin-like growth factors are not grossly affected by prior trypsinization of the adipocytes.These findings add further support to the concept that the insulin-like growth factors act on glucose metabolism and antilipolysis via the insulin receptor of the adipocyte.Insulin-like growth factors I and I1 purified from human serum [1,2] exert the same biological effects as insulin on adipose tissue and adipocytes : they stimulate glucose transport and net gas exchange, CO2 production and lipogenesis from glucose, and they inhibit lipolysis [3]. When compared on a molar basis, the biological potency of the two factors is z 35-times and 2 125-times less than that of insulin [3]. Adipocytes contain specific membrane binding sites for the insulin-like growth factors [3 -51. However, the latter have been shown to compete also with insulin for binding to the insulin receptor of the adipocyte [3 -61. Therefore, the question arises whethcr the acute insulin-like actions of the insulin-like growth factors are mediated via the insulin receptor or via their own specific acceptor sites. The correlation between the biological potencies of the three polypeptides and their competitive potencies at their respective membrane binding sites suggests that the insulin-like growth factors do exert their insulin-like effects on the adipocyte through the insulin receptor [3]. The present work was undertaken in order to obtain further evidence in favour or against this concept.

Cocaine abuse remains a significant worldwide health problem. Patients with cardiovascular toxicity from cocaine abuse frequently present to the emergency department for treatment. These patients may be tachycardic, hypertensive, agitated, and have chest pain. Several pharmacological options exist for treatment of cocaine-induced cardiovascular toxicity. For the past 3 decades, the phenomenon of unopposed α-stimulation after β-blocker use in cocaine-positive patients has been cited as an absolute contraindication, despite limited and inconsistent clinical evidence. In this review, the authors of the original studies, case reports, and systematic review in which unopposed α-stimulation was believed to be a factor investigate the pathophysiology, pharmacology, and published evidence behind the unopposed α-stimulation phenomenon. We also investigate other potential explanations for unopposed α-stimulation, including the unique and deleterious pharmacologic properties of cocaine in the absence of β-blockers. The safety and efficacy of the mixed β-/α-blockers labetalol and carvedilol are also discussed in relation to unopposed α-stimulation.

A B S T R A C T Nonsuppressible insulin-like activity extracted and purified from human serum (NSILA-S) mimics all insulin-like effects in vitro and, after injection, in vivo in the presence of excess insulin antibodies. However, there is no evidence that it exerts acute insulin-like effects in its native form in the circulation, where it is almost completely bound to a specific large molecular weight carrier protein. In this paper we show that partially purified NSILA-S-carrier protein, devoid ofendogenous insulin-like activity, inhibits the stimulatory effect of NSILA-S, but not of insulin, on 3-0-methylglucose transport and on lipogenesis from [U-14C]glucose in isolated rat fat cells. Concomitantly, it prevents binding of 125I-labeled NSILA-S to the insulin receptor and to the NSILA-Sbinding site.The following explanation is, therefore, offered for the absence of acute insulin-like effects of native NSILA-S in vivo: In native serum NSILA-S occurs alfmost exclusively as NSILA-S-carrier complex. Ac-cording to recent findings the passage of this complex through blood capillaries is restricted. The present results indicate that, in addition, it is metabolically inactive, or, at least, possesses reduced metabolic activity. The well-known phenomenon that whole serum, nevertheless, exerts pronounced nonsuppressible insulin-like effects on adipose tissue in vitro seems, therefore, to be mainly caused by the presence of a large molecular weight insulin-like protein not identical to the NSILA-S-carrier complex.

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