Studies on Plasma Glucagon Concentration in Maturity-Onset Diabetics with Autonomic Neuropathy

The mean fasting plasma immunoreactive glucagon (IRG) concentration in 25 non-insulin-dependent, maturity-onset diabetics (MODs) was 15.4 ± 3.1 pmol/L, which was not significantly different from the 16.8 ± 2.4 pmol/L in 17 normal controls of similar age. However, in seven MODs with autonomic neuropathy (AN) the mean fasting IRG concentration of 44.7 ± 4.4 was significantly greater than the 17.4 ±1.3 pmol/L in 18 MODs without neuropathy and compared with controls. We, therefore, investigated IRG concentrations in five age-matched, non-insulin-dependent MODs with AN and five without it. Plasma IRG concentrations were measured in the basal state on three separate occasions and in response to insulin and to a mixed meal. Fasting or basal IRG concentrations were measured in the morning with and without a preceding 12-h insulin infusion to determine the effects of reduction in fasting plasma glucose concentrations and after 12 h of nasogastric aspiration to exclude continued stimulation caused by delayed gastric emptying. In the select group of Subjects the mean basal plasma IRG concentration was raised above the normal in diabetics with AN (49.4 ± 5.1) and was 16.2 ± 2.1 in diabetics without AN, which was within normal limits. Neither 12 h of insulin infusion (0.5–0.8 U/h) nor 12 h of nasogastric aspiration altered basal IRG concentrations in either group. The maximum incremental IRG response to acute insulin administration (0.2 U/kg) in diabetics with AN was 6.8 ± 3.9, which was significantly impaired compared with 24.9 ± 4.8 in nine MODs without AN and with 26.3 ± 6.7 in five normal controls. The maximum increment in IRG response to acute insulin administration in diabetics with AN rose significantly to 32.8 ± 12.9 after 12 h of insulin infusion. Although the maximum IRG responses to a mixed meal were higher in both diabetic groups than in the normal controls, there was a delayed initial rise and persistent elevation in diabetics with AN. We suggest that (1) basal IRG concentrations may be dependent on the integrity of the autonomic nervous system in MODs; (2) MODs without AN seem to have a normal response to insulin-induced hypoglycemia, whereas in MODs with AN the response is impaired and can be corrected by an adequate degree of both insulinization and reduction in fasting blood glucose concentration; and (3) the maximum IRG response to a mixed meal is exaggerated in all MODs and is not dependent on the integrity of the autonomic nervous system, although the pattern of response may be altered in the presence Of AN.

[1]  L. Orci,et al.  Glucagon and the A cells. , 2010, Recent progress in hormone research.

[2]  A. Vinik,et al.  Inhibition of exaggerated gastrointestinal glucagon responses in chronic pancreatitis by somatostatin. , 1977, The Journal of clinical endocrinology and metabolism.

[3]  P. Raskin,et al.  Effects of Exogenous Hyperglucagonemia in Insulin-treated Diabetics , 1977, Diabetes.

[4]  P. Tothill,et al.  Gastric emptying in diabetic autonomic neuropathy. , 1977, Hormone and metabolic research. Supplement series.

[5]  J. Roth,et al.  Insulin receptor status in disease states of man. , 1977, Archives of internal medicine.

[6]  F. Goetz,et al.  Lack of Glucagon Response to Hypoglycemia in Diabetic Autonomic Neuropathy , 1977, Diabetes.

[7]  W. F. Taylor,et al.  Abnormalities of Endogenous Glucagon and Insulin in Unstable Diabetes , 1977, Diabetes.

[8]  P. Felig,et al.  Influence of physiologic hyperglucagonemia on basal and insulin-inhibited splanchnic glucose output in normal man. , 1976, The Journal of clinical investigation.

[9]  G. Weir,et al.  Glucagon Secretion from the Perfused Pancreas of Streptozotocin-treated Rats , 1976, Diabetes.

[10]  M. Lorenzi,et al.  Abnormal pancreatic glucagon secretion and postprandial hyperglycemia in diabetes mellitus. , 1975, JAMA.

[11]  A. Vinik,et al.  Immunoreactive Glucagon Responses to Intravenous Tolbutamide in Chronic Pancreatitis , 1975, Diabetes.

[12]  D. Hosking,et al.  Vagal impairment of gastric secretion in diabetic autonomic neuropathy. , 1975, British medical journal.

[13]  E. Tsalikian,et al.  Prevention of human diabetic ketoacidosis by somatostatin. Evidence for an essential role of glucagon. , 1975, The New England journal of medicine.

[14]  R. Unger,et al.  Plasma Glucagon Levels During Rapid Exsanguination with and without Adrenergic Blockade , 1975, Diabetes.

[15]  J. Palmer,et al.  The effect of adrenergic blockade on the glucagon responses to starvation and hypoglycemia in man. , 1974, The Journal of clinical investigation.

[16]  S. Bloom,et al.  Vagal control of glucagon release in man. , 1974, Lancet.

[17]  S. Woods,et al.  Neural control of the endocrine pancreas. , 1974, Physiological reviews.

[18]  D. Ewing,et al.  Testicular Pain Sensation in Diabetic Autonomic Neuropathy , 1974, British medical journal.

[19]  J. Gerich,et al.  Adrenergic modulation of pancreatic glucagon secretion in man. , 1974, The Journal of clinical investigation.

[20]  D. Ewing,et al.  Cardiovascular responses to sustained handgrip in normal subjects and in patients with diabetes mellitus: a test of autonomic function. , 1974, Clinical science and molecular medicine.

[21]  S. Bloom,et al.  The role of the autonomic innervation in the control of glucagon release during hypoglycaemia in the calf , 1974, The Journal of physiology.

[22]  D. Ewing,et al.  Vascular reflexes in diabetic autonomic neuropathy. , 1973, Lancet.

[23]  P. Watkins,et al.  Cardiac Denervation in Diabetes , 1973, British medical journal.

[24]  J. Gerich,et al.  Lack of Glucagon Response to Hypoglycemia in Diabetes: Evidence for an Intrinsic Pancreatic Alpha Cell Defect , 1973, Science.

[25]  S. Bloom,et al.  The role of the sympathetic innervation in the control of plasma glucagon concentration in the calf , 1973, The Journal of physiology.

[26]  J. Gerich,et al.  Stimulation of glucagon secretion by epinephrine in man. , 1973, The Journal of clinical endocrinology and metabolism.

[27]  D. M. Rocha,et al.  Abnormal pancreatic alpha-cell function in bacterial infections. , 1973, The New England journal of medicine.

[28]  S. Bloom,et al.  Release of glucagon, induced by stress. , 1973, Quarterly journal of experimental physiology and cognate medical sciences.

[29]  K. Buchanan,et al.  Abnormalities of glucagon metabolism in untreated diabetes mellitus. , 1972, Lancet.

[30]  L. Orci,et al.  The Beta Cell and Its Responses: Summarizing Remarks and Some Contributions from Geneva , 1972, Diabetes.

[31]  W. A. Müller,et al.  Abnormal Alpha Cell Function in Diabetics Response to Insulin , 1972, Diabetes.

[32]  W. A. Müller,et al.  Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. , 1970, The New England journal of medicine.

[33]  W. A. Müller,et al.  Studies of pancreatic alpha cell function in normal and diabetic subjects. , 1970, The Journal of clinical investigation.

[34]  R. Unger,et al.  Pancreatic glucagon secretion in normal and diabetic subjects. , 1969, The American journal of the medical sciences.

[35]  F. Hollander.  The insulin test for the presence of intact nerve fibers after vagal operations for peptic ulcer. , 1946, Gastroenterology.

[36]  W. Hoffman.  A RAPID PHOTOELECTRIC METHOD FOR THE DETERMINATION OF GLUCOSE IN BLOOD AND URINE , 1937 .

[37]  P. Raskin,et al.  Effects of exogenous glucagon in insulin treated diabetics , 1976 .

[38]  J. Gerich,et al.  Characterization of the glucagon response to hypoglycemia in man. , 1974, The Journal of clinical endocrinology and metabolism.

[39]  R. Unger,et al.  Hyperglucagonaemia after burns. , 1974, Lancet.

[40]  A. Vendsalu.  Studies on adrenaline and noradrenaline in human plasma. , 1960, Acta physiologica Scandinavica. Supplementum.

[41]  THE JOURNAL OF NEUROLOGY AND PSYCHIATRY TOPOGRAPHIC STUDIES OF DISTURBANCES OF SWEAT SECRETION AFTER COMPLETE LESIONS OF PERIPHERAL NERVES , 2022 .