Changes In Growth Hormone And Insulinlike Growth Factor1 In Hiv Infection

Disturbances in the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) axis have also been described in HIV infection. Decreased levels of IGF-1 have been noted in some malnourished individuals with HIV infection (37,38), but normal levels of IGF-1 were reported in two other groups of patients with prior weight loss (30,39). One potential explanation for these discrepant findings is that the patients in these latter two groups were studied during periods of relative clinical and...

Modulatory Effects Of Components Of The Somatotropic Axis On Sleep

Although the association between sleep and GH release has been well documented, there is also good evidence to indicate that components of the somatotropic axis are involved in regulating sleep quality. Although the roles of each hormone could not be identified, the findings of a recent study in transgenic mice with a deficiency in the somatotropic axis have been particularly convincing as a robust loss of non-REM sleep was demonstrated in these animals as compared to their wild-type...

Srif Receptor Subtypes

SRIF induces its biological actions by interacting with membrane-associated receptors. A number of studies had suggested that subtypes of SRIF receptors are expressed in the body (1). Studies on the pancreas suggested that SRIF 28 was much more potent than SRIF in blocking insulin secretion, whereas the peptides had similar potencies in controlling glucagon release (2), indicating that different receptors may be involved in mediating SRIF peptide effects on pancreatic hormone secretions....

Potential Indications

A clear role for the growth hormone secretagogues has yet to be demonstrated. The secretagogues have both potential advantages and disadvantages compared to recombinant human GH. GH replacement therapy requires parenteral administration and results in a nonphysiologic serum GH profile with often supraphysiologic levels. Particularly in older individuals, these characteristics may contribute to the poor clinical tolerability that has been reported in several clinical trials (49-52). In contrast,...

Insulin Resistance

Insulin resistance is a common condition and can be seen, for example, in NIDDM, obesity, and hypertension. The inter-relationship between insulin resistance and these conditions, as well as the exact mechanisms for insulin resistance, have not yet been fully clarified. It has recently been clear that GH-deficient adults are also insulin resistant in peripheral tissues (as measured using the hyperinsulinemic euglycemic clamp technique 67,68 ). In our study, glucose disposal rate (GDR) in the...

Insulinlike Growth Factor1 Igf1

It is generally assumed that most, of not all, of the protein-anabolic effects of rhGH are mediated by IGF-1 (50). Indeed, as described earlier, significant increases in plasma levels of IGF-1 have been observed following rhGH administration to patients with HIV-associated wasting (30,39). However, the magnitude of these increases is less than that seen in HIV-negative controls. These observations have prompted speculation that there may be a degree of rhGH resistance in patients with...

Animal Evaluations of MK0677

In additional dog studies, compound 44 (L-163,191) was active (a fourfold increase of peak GH over baseline) orally at 0.0675 mg kg (1 2 responded), at 0.125 mg kg (6 8 responded) and at 0.25 mg kg (7 8 responded). Following intravenous administration 4 4 dogs responded at the 0.025 mg kg level. In a balanced crossover study using eight beagles, compound 44 given orally increased peak GH concentrations in a dose responsive manner with a 5.3-fold increase at 0.25 mg kg, a 9.0-fold increase at...

Discovery Of The Benzolactam Secretagogues

With the renewed interest in potential clinical applications of GH, Merck researchers in 1988 became interested in discovering an orally active nonpeptidyl mimic peptidomimetic of GHRP-6. Extensive structure-activity relationships for GHRP-6 had already been published (5,8,9). Aromatic residues were favored at positions 2, 4, and 5 and a basic amino terminus was important for GH releasing activity. In addition, preliminary evidence at Merck suggested that the GHRP-6 receptor (hereafter referred...