The aim of the present study was to examine gene expression and protein concentrations of β 1 - and β 2 -adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. β-Adrenergic receptor mRNA levels were quantified by reverse transcription-PCR–HPLC. β-Adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8±0.8 kg (mean±S.E.M.) during diet treatment. There was a 34% decrease in the β 1 -adrenergic receptor mRNA level (0.92±0.09 compared with 0.61±0.06 amol/μg of DNA; P <0.002). β 2 -Adrenergic receptor mRNA did not decrease significantly. β 2 -Adrenergic receptor protein concentration decreased 37% (25.5±7.1 compared with 16.0±5.6 arbitrary units/ng of DNA; P =0.008), whereas β 1 -adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of β 1 -adrenergic receptor protein ( r =0.65, P <0.003) and changes in receptor protein concentration ( r =0.50, P =0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between β 1 -adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation.

The aim of the present study was to quantify β 2 -adrenoceptor protein content in adipose tissue during fasting, and to study the relationships between β 2 -adrenoceptor protein and mRNA levels and changes in metabolites related to lipolysis. Groups of male subjects with a body mass index of <25kg/m 2 or >30kg/m 2 fasted for 60h. Abdominal subcutaneous fat biopsies were analysed for receptor mRNA levels by reverse transcription–PCR–HPLC. The β 2 -adrenoceptor protein concentration was measured by Western blotting using fluorescence laser scanning for detection. The β 2 -adrenoceptor protein concentration per cell (on a DNA basis) was higher in obese subjects ( P <0.03). There were highly significant relationships between β 2 -adrenoceptor protein concentration and both body mass index and waist/hip ratio ( P <0.001 for both). Furthermore, there was an inverse relationship between the receptor protein concentration and the serum β-hydroxybutyrate level during fasting ( P <0.005). β 2 -Adrenoceptor protein levels decreased in both groups during fasting, to a similar degree. Basal β 2 -adrenoceptor mRNA levels were similar in the two groups, but there was a smaller increase in the obese group during fasting ( P <0.03). The increased β 2 -adrenoceptor protein level in obese subjects is likely to be related to the greater plasma membrane area of their adipocytes. The decrease during fasting may be due to increased binding of noradrenaline and subsequent internalization and degradation of the receptor. Elevated levels of less responsive β 2 -adrenoceptor protein in obese subjects may contribute to the development of obesity.

To test the hypothesis that changes in the expression of the glucocorticoid receptor (GCR) and the β 2 -adrenoceptor (β 2 -AR) contribute significantly to the abnormal glucose metabolism in skeletal muscle from patients with Type II diabetes, we have examined (1) the levels of total GCR (α+β isoforms), the α/α2 isoform of GCR and β 2 -AR mRNAs in skeletal muscle from insulin-resistant patients with Type II diabetes ( n = 10) and healthy controls ( n = 15), and (2) the effects of 8 weeks of intensive treatment on the whole-body glucose disposal rate and on total GCR, α/α2 GCR and β 2 -AR mRNA levels in diabetic patients. The total glucose disposal rate was measured by the euglycaemic hyperinsulinaemic (2m-unitsċmin -1 ċkg -1 ) clamp technique, and mRNA levels were assessed by reverse transcriptase-PCR and HPLC for separation of standard and unknown and quantification. Mean levels of total GCR and α/α2 GCR mRNAs were increased in patients with Type II diabetes when compared with control subjects [total GCR, 2.06±0.30 and 1.47±0.10 amol/ μ g of total RNA respectively ( P = 0.09); α/α2 GCR mRNA, 1.69±0.31and 0.92±0.09amol/ μ g of total RNA respectively ( P = 0.02)], whereas mRNA levels of the β isoform of GCR (total GCR minus α/α2 GCR) were decreased ( P = 0.006). β 2 -AR mRNA levels were comparable in diabetic patients and control subjects (0.53±0.05 and 0.45±0.02amol/ μ g of total RNA respectively; P = 0.2). Intensive treatment for 8 weeks was associated with improved glycaemic control ( P = 0.019), and during the clamp a 75% ( P = 0.001) increase in the whole-body insulin-stimulated glucose disposal rate was demonstrated. Total GCR ( P = 0.005), α/α2 GCR ( P = 0.005) and β 2 -AR ( P = 0.03) mRNA levels all decreased significantly after intensive insulin treatment. A close correlation was found between increments in glucose uptake during intensive treatment and decrements in skeletal muscle total GCR mRNA ( r = 0.95, P <0.001; multiple regression analysis), and between glucose uptake and α/α2 GCRm RNA levels ( r = 0.88, P <0.001; simple correlation). In conclusion, the abnormal regulation of GCR mRNA is likely to play a significant role in the insulin resistance observed in obese patients with Type II diabetes.

1. Previous histological studies have demonstrated partial reinnervation of the human transplanted kidney. However, it remains unknown whether this reinnervation is of any functional significance. 2. The effects of noradrenaline infusion (2 μgh −1 kg −1 ) and lower body negative pressure (−27 mmHg) on renal haemodynamics, sodium excretion and tubular function were investigated in 25 renal transplant recipients and 10 normal subjects. Sixteen of the transplant recipients had all been transplanted for more than 27 months, and nine had all been transplanted for less than 2 months. 3. After an overnight fast, the subjects were water-loaded, and clearance studies were performed with a 1 h baseline period, a 1 h period with noradrenaline infusion, another 1 h baseline period, and a final 1 h period with lower body negative pressure. 4. During noradrenaline infusion the relative decrease in effective renal plasma flow, glomerular filtration rate and clearance of lithium and sodium was significantly more pronounced in the long-term transplanted patients than in the control subjects. 5. Lower body negative pressure only depressed the glomerular filtration rate significantly in the control subjects. Further, the relative decrease in effective renal plasma flow and clearance of lithium and sodium was significantly greater in the control subjects than in the two groups of transplanted patients. 6. The present study thus demonstrated that in short- and long-term transplanted kidneys in man, supersensitivity to circulating noradrenaline and an inadequate response to lower body negative pressure was present. This strongly suggests that the human transplanted kidney remains functionally denervated.