Abstract. Hormonal responses (glucagon, pancreatic polypeptide and somatostatin) to iv glucagon, iv arginine, and ingestion of a mixed meal were investigated in 6 patients with insulin-dependent diabetes secondary to chronic pancreatitis without beta-cell function, in 8 Type I (insulin-dependent) diabetics without beta-cell function, and 8 healthy subjects. No significant differences were found between the two diabetic groups regarding glucagon responses to arginine and meal ingestion. In the patients with diabetes secondary to chronic pancreatitis compared with Type I diabetics and normal controls, the pancreatic polypeptide concentrations were significantly lower and somatostatin concentrations were significantly higher after glucagon, arginine and a mixed meal. Thus, pancreatic glucagon secretion was preserved in patients with insulin-dependent diabetes secondary to chronic pancreatitis, having no residual beta-cell function. These findings suggest that pancreatic glucagon deficiency is not absolute in insulin-dependent diabetes secondary to chronic pancreatitis. A high level of somatostatin may contribute to a lower blood glucose level in patients with chronic pancreatitis.
S. Larsen, J. Hilsted, B. Tronier and H. Worning
E. K. Philipsen, J. Myhre, S. Larsen, M. Damkjær Nielsen, J. J. Holst and J. Hilsted
To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the angonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed in 8 healthy subjects with and without concomitant beta-adrenoceptor blockade by iv propranolol. A significant correlation was found between increments in plasma adrenaline and plasma cyclic AMP in the experiments without beta-blockade; during concomitant beta-blockade the increase in plasma cyclic AMP concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and betahydroxy butyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man.
CH Gravholt, R Leth-Larsen, AL Lauridsen, S Thiel, TK Hansen, U Holmskov, RW Naeraa and JS Christiansen
OBJECTIVE: Studies in animals and humans indicate that growth hormone (GH) and insulin-like growth factor-I (IGF-I) modulate immune function. Recently, it was reported that GH therapy increased the level of mannan-binding lectin (MBL) in normal patients, and that treatment of acromegalics with pegvisomant decreased the levels of MBL. The effect on MBL was thought to be due to a specific action of GH, since IGF-I treatment did not affect MBL. Whether it is advantageous or not to have high or low levels of MBL is not known. Likewise, it is not clear how the modifications induced by GH affect immune function. In the present study we examined whether GH or hormone replacement therapy (HRT) in Turner syndrome (TS) influence the serum concentrations of MBL and two other proteins partaking in the innate immune defence, surfactant protein D (SP-D) and vitamin D binding protein (DBP). DESIGN: Study 1: a double-blind crossover study of 12 healthy TS adolescents examined during treatment with either placebo or GH for 2 months, and compared with a control group. Study 2: triple-blind crossover study of 9 healthy TS adolescents randomized to treatment with placebo, GH or GH+17beta-estradiol. Study 3: 60 adult TS patients (55 received HRT) compared with 59 age-matched controls. Study 4: 27 patients with TS were examined before and during sex hormone replacement with 17beta-estradiol and norethisterone and compared with age-matched controls (n=24). METHODS: Measurement of MBL, SP-D, DBP, and other inflammation markers. RESULTS: Study 1: the levels of MBL (P=0.002) and SP-D (P=0.012) increased during GH treatment, whereas no changes were observed in comparison with controls. DBP was unchanged by GH, but was significantly higher in TS compared with controls (P=0.017). Study 2: treatment with GH increased MBL (P=0.045) and SP-D (P=0.05) concentrations in TS, while treatment with GH+17beta-estradiol did not increase levels further. DBP was unchanged by treatment. Study 3: levels of MBL, SP-D, and DBP were similar in adult TS and control subjects. Study 4: DBP levels decreased in response to HRT, while MBL and SPD levels were unchanged. Levels of all three plasma proteins were similar to controls. CONCLUSION: We show that treatment with GH significantly increases MBL and SP-D concentrations in TS, while HRT marginally decreases DBP. Whether the present findings, suggesting a link between the endocrine and the immune system, have clinical consequences needs to be studied further.