Acute infections are accompanied by tissue insulin resistance, as manifested by worsening of metabolic control in diabetic patients and decreased glucose tolerance in non-diabetic subjects. To clarify the potential role of altered insulin receptor status in this phenomenon, we studied [125I]insulin binding to monocytes in 7 otherwise healthy subjects during acute bacterial and viral infections of moderate severity. The values were compared to those obtained after convalescence (five patients) and those of 24 normal subjects. Insulin binding during infection, at a time when insulin resistance was demonstrable, was indistinguishable from convalescent or normal values. Plasma glucose and insulin levels, the insulin to glucose ratio, as well as plasma GH, cortisol, and FFA were significantly elevated during infection, while plasma glucagon, epinephrine, and norepinephrine levels were normal. We conclude that insofar as monocyte receptors are representative of other tissues, insulin resistance in infection is mediated at the postreceptor level.

Human GH (hGH) consists of several molecular forms. Monomeric forms present in pituitary extracts include the single chain, 22,000 mol wt form (22K; hGH-B); a 20,000 mol wt, single chain variant (20K); three proteolytically cleaved, two-chain forms (hGH-C, -D, and -E), acetylated, deaminated, and slow-migrating forms. It is not known which of these forms are secreted in vivo or whether peripheral organs contribute to the interconversion between some of these hGH forms. To answer these questions, we studied the molecular forms of hGH excreted in urine from normal volunteers and from an acromegalic patient, as urinary hGH presumably reflects integrated plasma hGH. hGH was extracted from urine by hollow fiber diafiltration and concentration, followed by immunoadsorbent chromatography. The extracted hGH was examined by polyacrylamide gel electrophoresis under native as well as denaturing and reducing conditions and by isoelectric focusing. The predominant form of hGH in both normal urine and urine from the acromegalic patient was 22K, with small quantities (approximately 10%) of 20K and an unidentified acidic form also present. Cleaved forms with enhanced bioactivity (hGH-D and -E) and big hGH forms were not detectable. We conclude that 1) the pattern of urinary hGH suggests that spontaneously secreted and circulating hGH is composed of at least three hGH forms, with 22K predominating; 2) the pattern of urinary hGH is similar to that of plasma hGH after L-dopa stimulation; 3) hGH excreted in acromegaly is indistinguishable from hGH excreted by normal subjects; 4) only a minute fraction (less than 0.01%) of the hGH secreted reaches the final urine; and 5) renal interconversion among hGH forms does not appear quantitatively important.

No abstract

We have established a model for malignancy-associated humoral hypercalcemia (MAHH) in athymic mice, utilizing a human squamous cell lung carcinoma. In the present studies, we evaluated cis-platinum (DDP), a cytotoxic agent known to produce hypomagnesemia, and occasionally hypocalcemia, in the treatment of MAHH. Upon development of significant hypercalcemia, defined as serum calcium (Ca) greater than or equal to 11.5 mg/dl, tumor-bearing mice received either normal saline (NS) alone (1.5 ml/day, i.p.), or NS + DDP. The DDP was given as a single dose of 6 micrograms/g body weight i.p. Serum Ca was determined on day 6 in surviving mice (6 of 10 survived in the NS-alone group; 7 of 10 survived in the NS + DDP group). Serum Ca (mean +/- SE) decreased from 14.3 +/- 0.46 to a nadir of 12.7 +/- 0.33 mg/dl in the NS-alone group, and from 13.5 +/- 0.46 to a nadir of 10.4 +/- 0.48 mg/dl in the NS + DDP group. Nadir serum Ca levels were significantly lower in the NS + DDP group (P = 0.003). Three of 7 surviving NS + DDP mice achieved normocalcemia, whereas none of the NS-alone animals became normocalcemic. Tumor volumes increased in all animals. There was no change in the serum Ca in 5 tumor-free mice treated with NS + DDP. There were no significant differences in serum magnesium levels among groups of control mice, tumor-free mice treated with NS + DDP, tumor-bearing mice treated with NS + DDP, and tumor-bearing mice treated with NS-alone.(ABSTRACT TRUNCATED AT 250 WORDS)