Diabetologia

Lefebvre, P.; Luyckx, A.

doi: 10.1007/BF01223153pmid: 381082

125 16 16 6 6 P. J. Lefebvre A. S. Luyckx Division of Diabetes, Institute of Medicine University of Liège Belgium Conclusions The metabolic properties of glucagon, demonstrated both in vitro and in vivo , qualify it as a potential diabetogenic hormone. Plasma glucagon levels are usually elevated in diabetes, the highest levels being found in the absence of insulin. Numerous lines of evidence indicate that excess glucagon levels contribute to the metabolic abnormalities of diabetes. Nevertheless, diabetes can occur in the absence of glucagon (pancreatectomy in man). The absence of high intra-islet levels of insulin may explain the persistence of abnormally high plasma concentrations of glucagon in the diabetic receiving conventional insulin therapy. In maturity-onset type diabetes, the intimate mechanisms leading to abnormal circulating glucagon levels are completely unknown. A search for selective glucagon inhibitors represents an attractive new way in diabetes management.

Kalk, W.; Vinik, A.; Jackson, W.; Bank, S.

doi: 10.1007/BF01223154pmid: 467844

125 16 16 6 6 W. J. Kalk Dr. A. I. Vinik W. P. U. Jackson S. Bank Endocrine and Diabetes Research Group of the University of Cape Town Medical School and Groote Schuur Hospital Cape Town South Africa University of Michigan Medical Center 48109 Ann Arbor MI USA Summary The relationship between insulin responses to oral glucose and pancreatic exocrine function were examined in 15 patients with chronic pancreatitis. Good correlations were found between the insulin responses and exocrine pancreatic function measured as the concentrations of pancreatic enzymes in duodenal juice after intravenous cholecystokinin-pancreazymin (CCK-PZ). There appears to be a roughly parallel loss of endocrine and exocrine function in the course of chronic pancreatitis.

Campbell, L.; Kraegen, E.; Meler, H.; Lazarus, L.

doi: 10.1007/BF01223155pmid: 467845

125 16 16 6 6 L. V. Campbell E. W. Kraegen H. Meler L. Lazarus Garvan Institute of Medical Research St. Vincent's Hospital Sydney Australia Summary Twenty diabetic patients and fourteen normal volunteers received infusion of 2.4 U neutral porcine insulin/h until either the blood glucose level was stable, or until hypoglycaemia occurred. As previously reported (1) in the normal group the blood glucose stabilised at 2.8±0.1 mmol/l without any hypoglycaemic symptoms. There was an increase in blood levels of glucagon, cortisol and growth hormone as the blood glucose level fell, the mean peak increments being 167±33 pg/ml, 400±71 nmol/l and 29±7 mU/l, respectively. In ten of the diabetic subjects (Group A) the blood glucose level stabilised at 3.6±0.2 mmol/l during the insulin infusion, with peak increments in plasma glucagon (110±24pg/ml), cortisol (411±71 nmol/l) and growth hormone (22±6 mU/l), not significantly different from those in the normal subjects. These rises in hormone levels occurred during the last hour of infusion after normoglycaemia was reached and maintained. The ten remaining diabetics (Group B) developed symptoms of hypoglycaemia during the infusion. The peak increments in plasma glucagon (19±7 pg/ml), cortisol (183±36 nmol/l) and growth hormone (6±2 mU/l) in this latter group were significantly less than those in the other diabetic group or the normals. The absence of counter-regulatory hormonal responses in the Group B diabetics was related to the development of hypoglycaemia and may be the result of a dysfunction of hypothalamic gluco-regulatory centres.

Kalant, N.; Leibovici, T.; Rohan, I.; Ozaki, S.

doi: 10.1007/BF01223156pmid: 467846

125 16 16 6 6 N. Kalant T. Leibovici I. Rohan S. Ozaki Lady Davis Institute for Medical Research Jewish General Hospital Montreal Quebec Canada Summary A forearm perfusion technique was used to study glucose and insulin uptake by muscle. In normal subjects at glycaemic levels above 130 mg/100 ml, glucose uptake was independent of glucose concentration; it was directly related to insulin concentration but not to insulin uptake. In non-obese maturity-onset diabetic subjects, glucose uptake was dependent on glucose concentration and insulin uptake, but not on insulin concentration. In both groups there was a strong correlation between insulin concentration and insulin uptake; diabetics had a normal insulin uptake in relation to concentration. For a given change in insulin concentration the increase in glucose uptake was as great in diabetics as in controls, but the effect of insulin was mediated through a mechanism involving its uptake. Thus in the non-obese maturity-onset diabetic, forearm muscle is not insulin resistant. The apparent uptake of insulin measured by a radioimmunoassay in relation to its arterial concentration was lower and more variable for heterologous than for endogenous insulin. With a receptor assay the venous insulin concentrations were lower than with the immunoassay and differences in uptake between endogenous and exogenous insulin disappeared. It is concluded that in muscle exogenous insulin was less severely degraded than endogenous insulin.

Rushforth, N.; Miller, M.; Bennett, P.

doi: 10.1007/BF01223157pmid: 467847

125 16 16 6 6 N. B. Rushforth M. Miller P. H. Bennett Department of Biology and Biometry Case Western Reserve University Cleveland Ohio USA Department of Medicine Case Western Reserve University Cleveland Ohio USA Southwestern Field Studies Section, Epidemiology and Field Studies Branch National Institute of Arthritis, Metabolism, and Digestive Diseases Phoenix Arizona USA Summary The frequency distributions of both the fasting and two-hour post-load plasma glucose levels were bimodal in the Pima Indian population aged 25 years and over. The hyperglycaemic component of this distribution represents those with diabetes mellitus, as some 30 percent of this group had evidence of the specific vascular complications of the disease, whereas these abnormalities were virtually absent in those with lower glucose levels. The bimodal characteristics of the frequency distributions were utilized to define optimal criteria to separate those with and without diabetes. The sensitivity and specificity of these criteria for fasting and two-hour glucose levels were compared and were found to be similar. The fasting glucose determination, however, was more reproducible and stable, as well as being easier to obtain, indicating that it is the better measurement for diagnostic purposes. The optimal level for diagnosis of 7.5 mmol/l (136 mg/dl) for the fasting glucose and the equivalent two-hour value of 14 mmol/l (250 mg/dl), were higher than many previously recommended diagnostic levels. Nevertheless, there was no evidence that subjects with lower levels were at appreciable risk of developing the specific complications of diabetes. Subjects with impaired glucose tolerance (IGT), but without fasting hyperglycaemia, should not be diagnosed as having diabetes mellitus.

Naeije, R.; Badawi, M.; Vanhaelst, L.; Cornil, A.; L'Hermite, M.

doi: 10.1007/BF01223158pmid: 111989

125 16 16 6 6 R. Naeije M. Badawi L. Vanhaelst A. Cornil M. L'Hermite Intensive Care Unit St. Pierre Hospital Brussels Belgium Human Reproduction Unit Universities of Brussels Brussels Belgium Laboratory of Experimental Medicine Universities of Brussels Brussels Belgium Summary The prolactin response to 200 μg thyrotropin-releasing hormone (TRH) IV was studied in seven patients with diabetic ketoacidosis, at the start of the treatment, and again, in the same patients, five days after recovery, when the diabetes was well controlled. Normal basal prolactin concentrations and prolactin responses to TRH were found in both situations. There was no correlation between basal prolactin concentrations, or magnitude of prolactin responses to TRH, and any of the metabolic variables measured. These findings do not suggest a role for prolactin in the development of diabetic ketoacidosis.

Pickup, J.; Keen, H.; Parsons, J.; Alberti, K.

doi: 10.1007/BF01223159pmid: 467848

125 16 16 6 6 J. C. Pickup H. Keen J. A. Parsons K. G. M. M. Alberti Unit for Metabolic Medicine Guy's Hospital Medical School London Laboratory for Endocrine Physiology and Pharmacology National Institute for Medical Research Mill Hill, London Department of Clinical Biochemistry Royal Victoria Infirmary Newcastle-upon-Tyne England Summary Six insulin-dependent diabetics were studied on their conventional insulin treatment and during continuous, dual-rate, subcutaneous insulin infusion for periods of up to 4 days. Diabetic control, as assessed by mean plasma glucose, range of plasma glucose values, M-value or range of M-values was improved significantly in 5 patients (mean ± SD plasma glucose concentration on final infusion day 6.9±1.3 mmol/l, versus 11.3±3.2 mmol/l on conventional treatment). Once a suitable insulin dose was established blood glucose control could be maintained by continuous subcutaneous insulin infusion using the same daily infusion rate without frequent adjustment. In some cases this was less than the daily dose on the conventional treatment. However, glycaemic control in one “brittle” diabetic, with unpredictable swings in blood glucose on her normal regimen, was not improved by continuous subcutaneous insulin infusion. During the period tested there was no sepsis at the cannula implantation site and patients did not find the system uncomfortable or unduly inconvenient.

Appel, M.; Schibly, B.; Kamara, J.; Sorenson, R.

doi: 10.1007/BF01223160pmid: 467849

125 16 16 6 6 M. C. Appel B. A. Schibly J. A. Kamara R. L. Sorenson Department of Anatomy University of Minnesota School of Medicine Minneapolis Minnesota Departments of Pathology and Anatomy University of Massachusetts Medical School Worcester Massachusetts USA Summary The contribution of the adrenal gland to the development of the spontaneous syndrome of obesity and diabetes in Yellow-KK (Y-KK) mice was studied. Six-month old Y-KK mice exhibited hyperadrenocorticism and adrenal cortex enlargement. Light microscopic morphometric studies of Y-KK adrenals revealed an expanded volume of the adrenal cortex resulting from hyperplasia of zona fasciculata and reticularis cells. Ultrastructural studies revealed fewer lipid droplets, increased numbers of mitochondria and a more extensively developed Golgi system within zona fasciculata and reticularis cells. This cytological evidence of enhanced steroid biosynthetic and secretory activity was consistent with increased levels of plasma immunoreactive corticosterone. Structural and functional abnormalities of Y-KK adrenals were preceded by the development of obesity, hyperglycaemia and hyperinsulinaemia. It is unlikely, therefore, that the adrenal plays a causal role in the syndrome's pathogenesis, although, hyperadrenocorticism may be in part responsible for an exacerbation of the observed phenomena.

Dehaye, J.; Winand, J.; Poloczek, P.; Christophe, J.

doi: 10.1007/BF01223161pmid: 223927

125 16 16 6 6 J. P. Dehaye J. Winand P. Poloczek J. Christophe Department of Biochemistry, Medical School U. L. B. Brussels Belgium Summary In the epididymal adipose tissue of lean (+/+) C57 BL/6J mice deprived of calcium by ethy-leneglycol-bis-( β -aminoethylether) N,N′-tetraacetic acid (EGTA) treatment, corticotrophin-(1-24)-tetracosapeptide (ACTH)-stimulated lipolysis was abolished and peak levels of adenosine 3′,5′-cyclic monophosphate (cyclic AMP 1 ) were reduced by 80%. Calcium omission was less effective on isoproterenol-stimulated lipolysis and was ineffective on theophylline- or dibutyryl cyclic AMP-stimulated lipolysis. All EGTA effects were reversible. Lipolytic agents stimulated the net uptake of 45 Ca. This effect was inhibited by 2,4-dinitrophenol. The 45 Ca accumulated in response to lipolytic agents was largely La 3+ -nondisplaceable and was released with a half-life of 13 minutes under EGTA treatment. These results suggest that the mechanism promoting 45 Ca uptake in response to lipolytic agents was beyond cyclic AMP production in the adipose tissue of lean mice, but independent of free fatty acid release. In turn, intracellular as well as extracellular calcium facilitated maximal rates of lipolysis. In the adipose tissue of obese-hyperglycaemic (ob/ob) mice, the response to the lipolytic agents of glycerol release and cyclic AMP levels was reduced by 65% and 45 Ca uptake was not stimulated. A 1–2 hour preincubation of adipose tissue increased markedly the effect upon lipolysis and 45 Ca uptake, but not that of peak cyclic AMP levels of isoproterenol. It is concluded that the adipose tissue of ob/ob mice displayed a reversible impairment of 45 Ca uptake in response to lipolytic agents.