scholarly journals Effect of Glucagon-Like Peptide-1 on α- and β-Cell Function in C-Peptide-Negative Type 1 Diabetic Patients

2010 ◽  
Vol 24 (4) ◽  
pp. 875-875
Author(s):  
Urd Kielgast ◽  
Meena Asmar ◽  
Sten Madsbad ◽  
Jens J. Holst
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Diabetic Patients ◽  
Β Cell ◽  
C Peptide ◽  
Endogenous Insulin Secretion ◽  
Endogenous Insulin ◽  
Type 1 Diabetic Patients

Abstract Context: The mechanism by which glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion is uncertain, and it is not determined whether endogenous insulin is a necessary factor for this effect. Objective: Our objective was to characterize the α- and β-cell responses to GLP-1 in type 1 diabetic patients without residual β-cell function. Methods: Nine type 1 diabetic patients, classified as C-peptide negative by a glucagon test, were clamped at plasma glucose of 20 mmol/liter for 90 min with arginine infusion at time 45 min and concomitant infusion of GLP-1 (1.2 pmol/kg · min) or saline. Results: Infusion with GLP-1 increased C-peptide concentration just above the detection limit of 33 pmol/liter in one patient, but C-peptide remained immeasurable in all other patients. In the eight remaining patients, total area under the curve of glucagon was significantly decreased with GLP-1 compared with saline: 485 ± 72 vs. 760 ± 97 pmol/liter · min (P < 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 ± 21 and 137 ± 16 pmol/liter · min, with GLP-1 and saline, respectively, P < 0.05). Conclusions: In type 1 diabetic patients without endogenous insulin secretion, GLP-1 decreases the glucagon secretion as well as the arginine-induced glucagon response during hyperglycemia. GLP-1 induced endogenous insulin secretion in one of nine type 1 diabetic patients previously classified as being without endogenous insulin secretion.

scholarly journals Effect of Glucagon-Like Peptide-1 on α- and β-Cell Function in C-Peptide-Negative Type 1 Diabetic Patients

2010 ◽  
Vol 95 (5) ◽  
pp. 2492-2496 ◽  
Author(s):  
Urd Kielgast ◽  
Meena Asmar ◽  
Sten Madsbad ◽  
Jens J. Holst
Keyword(s):  
Insulin Secretion ◽  
Cell Function ◽  
Glucagon Secretion ◽  
Diabetic Patients ◽  
Β Cell ◽  
C Peptide ◽  
Endogenous Insulin Secretion ◽  
Endogenous Insulin ◽  
Type 1 Diabetic Patients

Abstract Context: The mechanism by which glucagon-like peptide-1 (GLP-1) suppresses glucagon secretion is uncertain, and it is not determined whether endogenous insulin is a necessary factor for this effect. Objective: To characterize the α- and β-cell responses to GLP-1 in type 1 diabetic patients without residual β-cell function. Methods: Nine type 1 diabetic patients, classified as C-peptide negative by a glucagon test, were clamped at plasma glucose of 20 mmol/liter for 90 min with arginine infusion at time 45 min and concomitant infusion of GLP-1 (1.2 pmol/kg · min) or saline. Results: Infusion with GLP-1 increased C-peptide concentration just above the detection limit of 33 pmol/liter in one patient, but C-peptide remained immeasurable in all other patients. In the eight remaining patients, total area under the curve of glucagon was significantly decreased with GLP-1 compared with saline: 485 ± 72 vs. 760 ± 97 pmol/liter · min (P < 0.001). In addition, GLP-1 decreased the arginine-stimulated glucagon release (incremental AUC of 103 ± 21 and 137 ± 16 pmol/liter · min, with GLP-1 and saline, respectively, P < 0.05). Conclusions: In type 1 diabetic patients without endogenous insulin secretion, GLP-1 decreases the glucagon secretion as well as the arginine-induced glucagon response during hyperglycemia. GLP-1 induced endogenous insulin secretion in one of nine type 1 diabetic patients previously classified as being without endogenous insulin secretion.

The addition of glipizide to insulin therapy in Type-II diabetic patients with secondary failure to sulfonylureas is useful only in the presence of a significant residual insulin secretion

1987 ◽  
Vol 116 (3) ◽  
pp. 364-372 ◽  
Author(s):  
Manuel Castillô ◽  
André J. Scheen ◽  
Giuseppe Paolisso ◽  
Pierre J. Lefébvre
Keyword(s):  
Insulin Secretion ◽  
Combined Therapy ◽  
Glucose Disposal ◽  
Diabetic Patients ◽  
Type Ii ◽  
Experimental Conditions ◽  
C Peptide ◽  
Endogenous Insulin Secretion ◽  
Endogenous Insulin ◽  
Secondary Failure

Abstract. The present study aimed at 1) investigating the effect of a combined insulin + glipizide treatment on the metabolic control (HbA1c levels) and insulin requirements (Biostator® assessment) in ten non-obese Type-II diabetic patients with recent secondary failure to sulfonylureas; and 2) characterizing the relative contributions of changes in endogenous insulin secretion (C-peptide response) and insulin sensitivity (insulin-induced glucose disposal in clamped conditions) to this effect. The patients were treated in a randomized cross-over order with either insulin alone or insulin + glipizide (3 × 10 mg/day) during two periods averaging 6 weeks each. Mean HbA1c levels were similar in both experimental conditions (8.2 ± 0.6 vs 7.9 ± 0.6%, NS). In fact, during the combined therapy, HbA1c levels decreased in five subjects (from 8.6 ± 0.7 to 7.1 ± 0.5%; 'responders'), but not in the five others ('non-responders'); the 20-h Biostator insulin infusion was significantly decreased in the responders (29%; P < 0.05), but not in the non-responders. Basal (0.271 ± 0.086 vs 0.086 ± 0.017 nmol/l; P < 0.05) and post-glucagon (0.468 ± 0.121 vs 0.180 ± 0.060 nmol/l; P < 0.05) C-peptide plasma levels were significantly higher in the responders than in the non-responders; in addition, glipizide significantly increased basal C-peptide concentrations in the responders only (+ 68%; P < 0.05). The insulininduced glucose disposal was significantly increased by glipizide in the responders (+ 23%; P < 0.05), but not in the non-responders; however, this difference could be due to higher plasma free insulin levels (+ 37%; P < 0.02) during the clamp with glipizide in the responders who showed persistent C-peptide stimulation. Thus, combining glipizide with insulin seems to be useful only in Type-II diabetic patients who still have a significant endogenous insulin secretion capable of being stimulated by this compound.

scholarly journals N-3 PUFA and Pregnancy Preserve C-Peptide in Women with Type 1 Diabetes Mellitus

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2082
Author(s):  
Josip Delmis ◽  
Marina Ivanisevic ◽  
Marina Horvaticek
Keyword(s):  
Type 1 Diabetes ◽  
Immune System ◽  
Pregnant Women ◽  
Cell Function ◽  
Insulin Production ◽  
Β Cell ◽  
C Peptide ◽  
Endogenous Insulin ◽  
Endogenous Insulin Production

Type 1 diabetes (T1DM) is an autoimmune disease characterized by the gradual loss of β-cell function and insulin secretion. In pregnant women with T1DM, endogenous insulin production is absent or minimal, and exogenous insulin is required to control glycemia and prevent ketoacidosis. During pregnancy, there is a partial decrease in the activity of the immune system, and there is a suppression of autoimmune diseases. These changes in pregnant women with T1DM are reflected by Langerhans islet enlargement and improved function compared to pre-pregnancy conditions. N-3 polyunsaturated fatty acids (n-3 PUFA) have a protective effect, affect β-cell preservation, and increase endogenous insulin production. Increased endogenous insulin production results in reduced daily insulin doses, better metabolic control, and adverse effects of insulin therapy, primarily hypoglycemia. Hypoglycemia affects most pregnant women with T1DM and is several times more common than that outside of pregnancy. Strict glycemic control improves the outcome of pregnancy but increases the risk of hypoglycemia and causes maternal complications, including coma and convulsions. The suppression of the immune system during pregnancy increases the concentration of C-peptide in women with T1DM, and n-3 PUFA supplements serve as the additional support for a rise in C-peptide levels through its anti-inflammatory action.

scholarly journals Residual β-Cell Function in Type 1 Diabetes Followed for 2 Years after 3C Study

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Kun Lin ◽  
Xiaoping Yang ◽  
Yixi Wu ◽  
Shuru Chen ◽  
Qiong Zeng
Keyword(s):  
Cell Function ◽  
Cox Regression ◽  
Diabetic Patients ◽  
Pancreatic Β Cell ◽  
Β Cell ◽  
C Peptide ◽  
Cox Regression Analysis ◽  
Β Cell Function ◽  
Age Of Diagnosis

Objective. To investigate the natural history and related factors of the pancreatic β-cell function in Chinese type 1 diabetic patients from 3C study Shantou center. Method. Stimulated C-peptide levels from follow-up data of 201 individuals in 3C study Shantou subgroup starting in 2012 were used. Residual β-cell function was defined as stimulated C − peptide   level ≥ 0.2   pmol / mL , on the basis of cut-points derived from the Diabetes Control and Complications Trial (DCCT). Results. 36.8% of patients had residual β-cell function, and the percentage was 68.2% in newly diagnosed diabetic patients. COX regression analysis indicated that the age of diagnosis, HbA1C level, and duration were independent factors of residual β-cell function in individuals with ≤5 years duration, but in those with duration ≥5 years, only the age of diagnosis was a predictor. The pancreatic β-cell function mainly declined in the first 5 years of the duration, and the rate of decline was correlated negatively with the duration and age of diagnosis. Receiver operating characteristic (ROC) analysis indicated that the cut-off point of stimulated C-peptide was 0.615 pmol/mL in patients with <5 years duration to have 7% HbA1c. Conclusion. Age at diagnosis was the strongest predictor for residual C-peptide. There was a more rapid decline of stimulated C-peptide in duration ≤5 years and younger patients. Therefore, intervention therapies of β-cells should start from the early stage, and the recommended target goal of stimulated C-peptide is 0.615 pmol/mL or above.

Impact of lack of suppression of glucagon on glucose tolerance in humans

1999 ◽  
Vol 277 (2) ◽  
pp. E283-E290 ◽  
Author(s):  
Pankaj Shah ◽  
Ananda Basu ◽  
Rita Basu ◽  
Robert Rizza
Keyword(s):  
Insulin Secretion ◽  
Glucose Concentration ◽  
Cell Function ◽  
Hormone Secretion ◽  
Glucose Production ◽  
Glucagon Secretion ◽  
Β Cell ◽  
Β Cell Function ◽  
Glucagon Suppression

People with type 2 diabetes have defects in both α- and β-cell function. To determine whether lack of suppression of glucagon causes hyperglycemia when insulin secretion is impaired but not when insulin secretion is intact, twenty nondiabetic subjects were studied on two occasions. On both occasions, a “prandial” glucose infusion was given over 5 h while endogenous hormone secretion was inhibited. Insulin was infused so as to mimic either a nondiabetic ( n = 10) or diabetic ( n = 10) postprandial profile. Glucagon was infused at a rate of 1.25 ng ⋅ kg−1 ⋅ min−1, beginning either at time zero to prevent a fall in glucagon (nonsuppressed study day) or at 2 h to create a transient fall in glucagon (suppressed study day). During the “diabetic” insulin profile, lack of glucagon suppression resulted in a marked increase ( P < 0.002) in both the peak glucose concentration (11.9 ± 0.4 vs. 8.9 ± 0.4 mmol/l) and the area above basal of glucose (927 ± 77 vs. 546 ± 112 mmol ⋅ l−1 ⋅ 6 h) because of impaired ( P < 0.001) suppression of glucose production. In contrast, during the “nondiabetic” insulin profile, lack of suppression of glucagon resulted in only a slight increase ( P< 0.02) in the peak glucose concentration (9.1 ± 0.4 vs. 8.4 ± 0.3 mmol/l) and the area above basal of glucose (654 ± 146 vs. 488 ± 118 mmol ⋅ l−1 ⋅ 6 h). Of interest, when glucagon was suppressed, glucose concentrations differed only minimally during the nondiabetic and diabetic insulin profiles. These data indicate that lack of suppression of glucagon can cause substantial hyperglycemia when insulin availability is limited, therefore implying that inhibitors of glucagon secretion and/or glucagon action are likely to be useful therapeutic agents in such individuals.

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