Hormonal responses to insulin infusion in diabetes mellitus

Campbell, Lesley V.; Kraegen, Edward W.; Meler, H.; Lazarus, L.

doi:10.1007/bf01223155

Cited by 28 publications

(31 citation statements)

References 17 publications

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“…However, greater and more prolonged hypoglycemia generally occurs in patients with IDDM (6-12) and is frequently followed by rebound hyperglycemia (6,12). The greater hypoglycemia in IDDM appears to be largely explicable on the basis ofa prolonged half-life of insulin, due to the presence of insulin antibodies (7,12) along with more severe impairment in neuroendocrine counterregulatory responses, since, for example, plasma glucagon responses are generally absent and plasma epinephrine responses are frequently blunted in IDDM (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), whereas in patients with NIDDM in the present study plasma glucagon responses were merely blunted and plasma epinephrine responses were similar to those ofthe nondiabetic subjects. It should be pointed out, however, that the NIDDM patients examined in the present study had relatively mild diabetes ofshort duration, and in those treated with insulin, insulin antibody binding was quite low.…”

Section: Resultsmentioning

confidence: 99%

“…In the four previous studies that we are aware of that dealt with this issue, (3,(13)(14)(15), no consensus was reached concerning the appropriateness of counterregulatory hormone responses (3,(13)(14)(15). Furthermore, no data are presently available concerning changes in glucose production and glucose utilization or the ability to restore euglycemia.…”

Section: Introductionmentioning

confidence: 94%

“…It is well established that glucose counterregulatory mechanisms are abnormal in insulin-dependent diabetes mellitus (IDDM)' (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). During insulin-induced hypoglycemia in patients with this disorder, plasma glucagon generally does not increase (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12); plasma epinephrine responses are frequently blunted (5)(6)(7)(8)(9)(10)(11)(12), even in the absence of clinically detectable autonomic neuropathy (6,(7)(8)(9)(10)(11)(12); and sometimes plasma growth hormone and cortisol responses are impaired (3,8,11,12).…”

Section: Introductionmentioning

confidence: 99%

“…During insulin-induced hypoglycemia in patients with this disorder, plasma glucagon generally does not increase (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12); plasma epinephrine responses are frequently blunted (5)(6)(7)(8)(9)(10)(11)(12), even in the absence of clinically detectable autonomic neuropathy (6,(7)(8)(9)(10)(11)(12); and sometimes plasma growth hormone and cortisol responses are impaired (3,8,11,12). As a result ofthese abnormalities there is an exaggerated suppression of hepatic glucose production (4,8,9,12), which may lead to severe and prolonged hypoglycemia (8,9,12).…”

Section: Introductionmentioning

confidence: 99%

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Defective glucose counterregulation after subcutaneous insulin in noninsulin-dependent diabetes mellitus. Paradoxical suppression of glucose utilization and lack of compensatory increase in glucose production, roles of insulin resistance, abnormal neuroendocrine responses, and islet paracrine interactions.

Bolli¹,

Tsalikian²,

Haymond³

et al. 1984

J. Clin. Invest.

105

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Abs tract. To characterize glucose counterregulatory mechanisms in patients with noninsulin-dependent diabetes mellitus (NIDDM) and to test the hypothesis that the increase in glucagon secretion during hypoglycemia occurs primarily via a paracrine islet A-B cell interaction, we examined the effects of a subcutaneously injected therapeutic dose ofinsulin (0.15 U/kg) on plasma glucose kinetics, rates of glucose production and utilization, and their relationships to changes in the circulating concentrations of neuroendocrine glucoregulatory factors (glucagon, epinephrine, norepinephrine, growth hormone, and cortisol), as well as to changes in endogenous insulin secretion in 13 nonobese NIDDM patients with no clinical evidence of autonomic neuropathy. Compared with 11 age-weight matched nondiabetic volunteers in whom euglycemia was restored primarily by a compensatory increase in glucose production, in the diabetics there was no compensatory increase in glucose production (basal 2.08±0. plasma insulin concentrations were similar in both groups (peak values 22±2 vs. 23±2 ,U/ml in diabetics and nondiabetics, respectively). This abnormality in glucose production was nearly completely compensated for by a paradoxical decrease in glucose utilization after injection of insulin (basal 2.11±0.03 -+ 1.86±0.06 mg/kg per min at 2/2 h in diabetics vs. basal 2.08±0.04 --2.39±0.11 mg/ kg per min at 2'/2 h nondiabetics, P < 0.01), which could not be accounted for by differences in plasma glucose concentrations; the net result was a modest prolongation of hypoglycemia. Plasma glucagon (area under the curve [AUCG above base line, 12±3 vs. 23±3 mg/ml. 12 h in nondiabetics, P < 0.05), cortisol (AUC 2.2±0.5 vs. 4.0±0.7 mg/dl-12 h in nondiabetics, P < 0.05), and growth hormone (AUC 1.6±0.4 vs. 2.9±0.4 ,g/ml. 12 h in nondiabetics, P < 0.05) responses in the diabetics were decreased 50% while their plasma norepinephrine responses (AUC 49±12 vs. 21±5 ng/ml-12 h in nondiabetics, P < 0.05) were increased twofold (P < 0.05) and their plasma epinephrine responses were similar to those ofthe nondiabetics (AUC 106±17 vs. 1 12±10 ng/ml -12 h in nondiabetics). In both groups of subjects, increases in plasma glucagon were inversely correlated with plasma glucose concentrations (r = -0.80 in both groups, P < 0.01) and suppression of endogenous insulin secretion (r = -0.57 in nondiabetics and -0.64 Volume 73, June 1984, 1532-1541 Our results thus indicate that glucose counterregulatory mechanisms are abnormal in patients with NIDDM: impaired glucagon, growth hormone, cortisol, and perhaps epinephrine responses during hypoglycemia could all contribute to a lack of compensatory increase in glucose production while near normal (epinephrine) and increased (norepinephrine) release ofcatecholamines in the presence of resistance to insulin in peripheral tissues may explain the accompanying suppression of glucose utilization. The inverse relationship between increases in plasma glucagon and suppression of insulin secretion observed during hypoglycemia in ...

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Defective glucose counterregulation after subcutaneous insulin in noninsulin-dependent diabetes mellitus. Paradoxical suppression of glucose utilization and lack of compensatory increase in glucose production, roles of insulin resistance, abnormal neuroendocrine responses, and islet paracrine interactions.

Bolli¹,

Tsalikian²,

Haymond³

et al. 1984

J. Clin. Invest.

105

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“…However, whether recipients undergo alterations in counterregulatory hormonal responses to glycopenia, or improvement in counterregulation of hypoglycemia, has not been determined. These are important considerations because type I diabetic patients commonly have defective glucagon and epinephrine responses to hypoglycemia and, consequently, deranged counterregulation of hypoglycemia with its attendant risks (8)(9)(10)(11)(12)(13). Therefore, presence or absence of improvement in these responses are highly relevant factors in the evaluation of the overall benefits of pancreas transplantation.…”

mentioning

confidence: 99%

Glucagon, catecholamine and pancreatic polypeptide secretion in type I diabetic recipients of pancreas allografts.

Diem¹,

Redmon²,

Abid

et al. 1990

J. Clin. Invest.

134

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After successful pancreas transplantation, recipients with type I diabetes mellitus achieve a return to normal fasting plasma glucose levels, normal oral glucose tolerance tests, and normal levels of HbA,C (1-7). However, whether recipients undergo alterations in counterregulatory hormonal responses to glycopenia, or improvement in counterregulation of hypoglycemia, has not been determined. These are important considerations because type I diabetic patients commonly have defective glucagon and epinephrine responses to hypoglycemia and, consequently, deranged counterregulation of hypoglycemia with its attendant risks (8-13). Therefore, presence or absence of improvement in these responses are highly relevant factors in the evaluation of the overall benefits of pancreas transplantation. Moreover, since the transplanted pancreas is denervated and since islet alpha cell and pancreatic polypeptide cell function is neurally modulated, investigation of pancreas recipients offers a unique opportunity to assess regulation ofglucagon and pancreatic polypeptide secretion from the pancreas in humans in the setting of absent central nervous system input into the islet.To evaluate hormonal counterregulation of hypoglycemia in patients with type I diabetes mellitus who have received successful pancreas allografts, we have examined glucose, glucagon, pancreatic polypeptide, and catecholamine responses during insulin-induced hypoglycemia. We have also assessed glucagon and pancreatic polypeptide responsivity to direct stimulators of alpha and pancreatic polypeptide cells (arginine and secretin, respectively) to ascertain whether possible alterations in secretory responses in pancreas recipients are specific for hypoglycemic signaling or more general in nature. In this study, the responses of pancreas recipients were compared with responses of patients with similar durations of type I diabetes mellitus, who had not received pancreas transplantation, and to nondiabetic control subjects. MethodsSubjects. 38 type I diabetic recipients of pancreas allografts with iliac vessel anastomoses and with intact native pancreases who had been transplanted between 3 and 60 mo previously were studied (Table I). All recipients were normoglycemic, had normal hemoglobin A,C levels and mildly elevated serum creatinine levels, and none were receiving exogenous insulin or other medication for diabetes. Immunosuppression was achieved with the triple-drug regimen of azathioprine, cyclosporine, and prednisone (14). 54 patients with type I diabetes and with similar age, sex distribution, body-mass index, serum creatinine levels, and duration ofdiabetes, as well as 26 normal volunteers of similar age, sex distribution, and body-mass index, were studied to obtain control data. All subjects were admitted to the University

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Overview of counterregulation and its abnormalities in diabetes mellitus and other conditions

Gerich

Campbell

1988

Diabetes Metab. Rev.

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Hormonal responses to insulin infusion in diabetes mellitus

Cited by 28 publications

References 17 publications

Glucagon, catecholamine and pancreatic polypeptide secretion in type I diabetic recipients of pancreas allografts.

Overview of counterregulation and its abnormalities in diabetes mellitus and other conditions

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