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The uptake of 2-[3H]deoxyglucose, a non-metabolisable derivative of glucose, was studied in resting and contracting muscle. An isolated phrenic nerve/hemidiaphragm preparation of the mouse was used, and contractions of the muscle were elicited by electrical stimulation of the nerve. beta-Endorphin stimulated the uptake of 2-deoxyglucose in resting diaphragm muscle. The rate of uptake in the presence of the optimum concentration of beta-endorphin was similar to that in the presence of the optimum concentration of insulin over the short incubation period. beta-Endorphin also stimulated the uptake of 2-deoxyglucose in contracting muscle, but the optimum concentration of the peptide for this effect was three orders of magnitude lower than in resting muscle. The optimum concentration for insulin, however, was similar in resting and contracting muscle. An analogue of the C-terminal tetrapeptide of beta-endorphin also stimulated 2-deoxyglucose uptake, but this peptide was equally efficacious in resting and contracting muscle. It is suggested that beta-endorphin, which is released into the circulation during exercise, may have a hormonal action to increase the uptake of glucose during muscular activity. This peptide or its metabolites may be partly responsible for the insulin-independent uptake of glucose during exercise.

Somatostatin analogues may be useful novel agents in the systemic treatment of advanced colorectal cancer, as somatostatin inhibits proliferation in a wide variety of cell types. Here, we report the expression profiles of somatostatin receptor mRNAs in 32 pairs of malignant and normal colonic epithelia. Receptor subtype 2 (hSSTR2) mRNA was detected throughout nearly 90% of both malignant and normal tissue by reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization. Subtype 5 (hSSTR5) mRNA was detected in 46% and 45% of tumour and mucosal samples respectively, but in 75% (9/12) of early-stage tumours (tubulovillous adenomas, Dukes' A and B) compared with 31% (5/16) of late-stage tumours (Dukes' C and 'D' tumours), 0.05>P>0.025 (chi2 with Yates' correction). There was also reduced expression of hSSTR5 in samples of metastatic tumour (11%, 1/9) compared with all tumour samples (56%, 18/32) 0.025>P>0.01 (chi2 with Yates' correction). Other hSSTRs (1, 3 and 4) were expressed infrequently. Thus, hSSTR2 expression is retained after malignant transformation in colonic epithelium and, although it may potentially be a target for antiproliferative therapy, its ubiquitous expression militates against this. hSSTR5 warrants investigation as a tumour suppressor.

Somatostatin is a widely distributed inhibitory peptide with growth-inhibitory effects in several human tumours, including breast cancer, raising the possibility that it may have therapeutic potential. The effects of somatostatin are mediated via a family of cell-surface receptors that differ in their tissue distribution, pharmacological properties and intracellular response mediators, suggesting that they mediate different functions of the peptide. We have analysed the expression of somatostatin receptor subtype (SSTR1-5) mRNA in normal and malignant breast tissue. Receptor expression was analysed by reverse transcription-polymerase chain reaction (RT-PCR) using receptor subtype-specific primers and by in situ hybridization (ISH) with riboprobes synthesized by in vitro transcription of cloned PCR products. A total of 51 breast carcinomas, 36 samples of matched normal tissue, two axillary node metastases and eight normal/benign breast tissue samples were analysed. SSTR2 expression was ubiquitous in both normal and malignant breast tissue. Expression of SSTR5 was detected in approximately one-third of tumour and normal tissue, but fewer than 13% of all tissues expressed SSTR1, 3 and 4. These data suggest that SSTR2 gene expression is ubiquitous in breast cancer. Although this is unlikely to have diagnostic or prognostic significance, SSTR2-specific somatostatin analogues may have therapeutic potential in breast cancer.