Jens J U U L Holst (original) (raw)
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Papers by Jens J U U L Holst
The American Journal of Clinical Nutrition, 2005
The American Journal of Clinical Nutrition, 2004
The Journal of Clinical Endocrinology & Metabolism, 2016
Kidney International, 2013
The Journal of Clinical Endocrinology & Metabolism, 2001
The Journal of Clinical Endocrinology & Metabolism, 2009
The Journal of Clinical Endocrinology & Metabolism, 2003
The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved ... more The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved in typical middle-aged, obese, insulin-resistant type 2 diabetic patients, whereas a defective amplification of the so-called late-phase plasma insulin response (20–120 min) to glucose by the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is seen in these patients. The aim of the present investigation was to evaluate plasma insulin and C-peptide responses to GLP-1 and GIP in five groups of diabetic patients with etiology and phenotype distinct from the obese type 2 diabetic patients. We studied (six in each group): 1) patients with diabetes mellitus secondary to chronic pancreatitis; 2) lean type 2 diabetic patients (body mass index < 25 kg/m2); 3) patients with latent autoimmune diabetes in adults; 4) diabetic patients with mutations in the HNF-1α gene [maturity-onset diabetes of the young (MODY)3]; and 5) newly diagnosed type 1 diabetic patients. All par...
The Journal of Clinical Endocrinology & Metabolism, 2003
![Research paper thumbnail of Effects of subcutaneous glucagon-like peptide 1 (GLP-1 [7-36 amide]) in patients with NIDDM](https://attachments.academia-assets.com/120483376/thumbnails/1.jpg)
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Diabetes, 2014
Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgrou... more Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of nonautoimmune diabetes, constituting 1–2% of all diabetes. Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and intravenous glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), respectively, and in matched healthy control subjects. Both MODY groups exhibited glucose intolerance after oral glucose (most pronounced in patients with HNF1A-diabetes), but only patients with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon responses to OGTT. Both groups of patients with diabetes showed normal suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes, similar to type 2 diabetes, is characterized by an impaired incretin effect and inappropriate glucagon responses, whereas incretin effect and gl...
Diabetes, 2004
A reduced insulinotropic effect of gastric inhibitory polypeptide (GIP) is a characteristic of pa... more A reduced insulinotropic effect of gastric inhibitory polypeptide (GIP) is a characteristic of patients with type 2 diabetes. It was the aim of this study to determine the response of insulin secretion to different GIP doses administered by intravenous bolus injection and via continuous infusion in both healthy subjects and patients with type 2 diabetes. Eight patients with type 2 diabetes and eight healthy subjects participated in a 240-min hyperglycemic clamp (140 mg/dl) with intravenous infusion of placebo, GIP at a low dose, and GIP at a high dose, each administered continuously over 60 min. Boluses of placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at 0, 60, and 120 min, respectively. Capillary and venous blood was drawn for glucose, insulin, C-peptide, and GIP. Plasma insulin and C-peptide concentrations were lower in patients than in control subjects during all infusion periods. GIP bolus administration evoked a significant increase in plasma insulin l...
Diabetes, 2001
In patients with type 2 diabetes, gastric inhibitory polypeptide (GIP) has lost much of its insul... more In patients with type 2 diabetes, gastric inhibitory polypeptide (GIP) has lost much of its insulinotropic activity. Whether this is similar in first-degree relatives of patients with type 2 diabetes is unknown. A total of 21 first-degree relatives, 10 patients with type 2 diabetes, and 10 control subjects (normal oral glucose tolerance) were examined. During a hyperglycemic “clamp” (140 mg/dl for 120 min), synthetic human GIP (2 pmol · kg−1 · min−1) was infused intravenously (30–90 min). With exogenous GIP, patients with type 2 diabetes responded with a lower increment (Δ) in insulin (P = 0.0003) and C-peptide concentrations (P < 0.0001) than control subjects. The GIP effects in first-degree relatives were diminished compared with control subjects (Δ insulin: P = 0.04; Δ C-peptide: P = 0.016) but significantly higher than in patients with type 2 diabetes (P ≤ 0.05). The responses over the time course were below the 95% CI derived from control subjects in 7 (insulin) and 11 (C-pe...
American Journal of Physiology-Endocrinology and Metabolism, 2004
The available evidence suggests that about two-thirds of the insulin response to an oral glucose ... more The available evidence suggests that about two-thirds of the insulin response to an oral glucose load is due to the potentiating effect of gut-derived incretin hormones. The strongest candidates for the incretin effect are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). In patients with type 2 diabetes, however, the incretin effect is lost or greatly impaired. It is hypothesized that this loss explains an important part of the impaired insulin secretion in patients. Further analysis of the incretin effects in patients has revealed that the secretion of GIP is near normal, whereas the secretion of GLP-1 is decreased. On the other hand, the insulintropic effect of GLP-1 is preserved, whereas the effect of GIP is greatly reduced, mainly because of a complete loss of the normal GIP-induced potentiation of second-phase insulin secretion. These two features, therefore, explain the incretin defect of type 2 diabetes. Strong support for the hypothesis...
American Journal of Physiology-Endocrinology and Metabolism, 2009
We investigated the role of glucose-dependent insulintropic polypeptide (GIP) in the regulation o... more We investigated the role of glucose-dependent insulintropic polypeptide (GIP) in the regulation of gastric emptying (GE), appetite, energy intake (EI), energy expenditure (EE), plasma levels of triglycerides (TAG), and free fatty acids (FFA) in humans. First, 20 healthy males received intravenous infusion of GIP (0.8 pmol·kg−1·min−1) or saline for 300 min during and after a fixed meal ( protocol 1). GE was measured using paracetamol, appetite sensations using visual analog scales, EE using indirect calorimetry, and EI during a subsequent ad libitum meal (at 300 min). Next, 10 healthy males received intravenous infusions of Intralipid, glucose, or Intralipid plus glucose, with and without GIP (1.5 pmol·kg−1·min−1) for 300 min ( protocol 2). In protocol 1, GIP did not have any effect on GE, EI, EE, removal of TAG, or FFA and did not influence the subjective feeling of hunger, satiety, fullness or prospective food consumption compared with saline. In protocol 2, no difference was seen ...
The American Journal of Clinical Nutrition, 2009
The American Journal of Clinical Nutrition, 2005
The American Journal of Clinical Nutrition, 2004
The Journal of Clinical Endocrinology & Metabolism, 2016
Kidney International, 2013
The Journal of Clinical Endocrinology & Metabolism, 2001
The Journal of Clinical Endocrinology & Metabolism, 2009
The Journal of Clinical Endocrinology & Metabolism, 2003
The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved ... more The effect of the insulinotropic incretin hormone, glucagon-like peptide-1 (GLP-1), is preserved in typical middle-aged, obese, insulin-resistant type 2 diabetic patients, whereas a defective amplification of the so-called late-phase plasma insulin response (20–120 min) to glucose by the other incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), is seen in these patients. The aim of the present investigation was to evaluate plasma insulin and C-peptide responses to GLP-1 and GIP in five groups of diabetic patients with etiology and phenotype distinct from the obese type 2 diabetic patients. We studied (six in each group): 1) patients with diabetes mellitus secondary to chronic pancreatitis; 2) lean type 2 diabetic patients (body mass index < 25 kg/m2); 3) patients with latent autoimmune diabetes in adults; 4) diabetic patients with mutations in the HNF-1α gene [maturity-onset diabetes of the young (MODY)3]; and 5) newly diagnosed type 1 diabetic patients. All par...
The Journal of Clinical Endocrinology & Metabolism, 2003
Diabetes, 2014
Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgrou... more Maturity-onset diabetes of the young (MODY) is a clinically and genetically heterogeneous subgroup of nonautoimmune diabetes, constituting 1–2% of all diabetes. Because little is known about incretin function in patients with MODY, we studied the incretin effect and hormone responses to oral and intravenous glucose loads in patients with glucokinase (GCK)-diabetes (MODY2) and hepatocyte nuclear factor 1α (HNF1A)-diabetes (MODY3), respectively, and in matched healthy control subjects. Both MODY groups exhibited glucose intolerance after oral glucose (most pronounced in patients with HNF1A-diabetes), but only patients with HNF1A-diabetes had impaired incretin effect and inappropriate glucagon responses to OGTT. Both groups of patients with diabetes showed normal suppression of glucagon in response to intravenous glucose. Thus, HNF1A-diabetes, similar to type 2 diabetes, is characterized by an impaired incretin effect and inappropriate glucagon responses, whereas incretin effect and gl...
Diabetes, 2004
A reduced insulinotropic effect of gastric inhibitory polypeptide (GIP) is a characteristic of pa... more A reduced insulinotropic effect of gastric inhibitory polypeptide (GIP) is a characteristic of patients with type 2 diabetes. It was the aim of this study to determine the response of insulin secretion to different GIP doses administered by intravenous bolus injection and via continuous infusion in both healthy subjects and patients with type 2 diabetes. Eight patients with type 2 diabetes and eight healthy subjects participated in a 240-min hyperglycemic clamp (140 mg/dl) with intravenous infusion of placebo, GIP at a low dose, and GIP at a high dose, each administered continuously over 60 min. Boluses of placebo, 20 pmol GIP/kg, and 80 pmol GIP/kg were injected intravenously at 0, 60, and 120 min, respectively. Capillary and venous blood was drawn for glucose, insulin, C-peptide, and GIP. Plasma insulin and C-peptide concentrations were lower in patients than in control subjects during all infusion periods. GIP bolus administration evoked a significant increase in plasma insulin l...
Diabetes, 2001
In patients with type 2 diabetes, gastric inhibitory polypeptide (GIP) has lost much of its insul... more In patients with type 2 diabetes, gastric inhibitory polypeptide (GIP) has lost much of its insulinotropic activity. Whether this is similar in first-degree relatives of patients with type 2 diabetes is unknown. A total of 21 first-degree relatives, 10 patients with type 2 diabetes, and 10 control subjects (normal oral glucose tolerance) were examined. During a hyperglycemic “clamp” (140 mg/dl for 120 min), synthetic human GIP (2 pmol · kg−1 · min−1) was infused intravenously (30–90 min). With exogenous GIP, patients with type 2 diabetes responded with a lower increment (Δ) in insulin (P = 0.0003) and C-peptide concentrations (P < 0.0001) than control subjects. The GIP effects in first-degree relatives were diminished compared with control subjects (Δ insulin: P = 0.04; Δ C-peptide: P = 0.016) but significantly higher than in patients with type 2 diabetes (P ≤ 0.05). The responses over the time course were below the 95% CI derived from control subjects in 7 (insulin) and 11 (C-pe...
American Journal of Physiology-Endocrinology and Metabolism, 2004
The available evidence suggests that about two-thirds of the insulin response to an oral glucose ... more The available evidence suggests that about two-thirds of the insulin response to an oral glucose load is due to the potentiating effect of gut-derived incretin hormones. The strongest candidates for the incretin effect are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1). In patients with type 2 diabetes, however, the incretin effect is lost or greatly impaired. It is hypothesized that this loss explains an important part of the impaired insulin secretion in patients. Further analysis of the incretin effects in patients has revealed that the secretion of GIP is near normal, whereas the secretion of GLP-1 is decreased. On the other hand, the insulintropic effect of GLP-1 is preserved, whereas the effect of GIP is greatly reduced, mainly because of a complete loss of the normal GIP-induced potentiation of second-phase insulin secretion. These two features, therefore, explain the incretin defect of type 2 diabetes. Strong support for the hypothesis...
American Journal of Physiology-Endocrinology and Metabolism, 2009
We investigated the role of glucose-dependent insulintropic polypeptide (GIP) in the regulation o... more We investigated the role of glucose-dependent insulintropic polypeptide (GIP) in the regulation of gastric emptying (GE), appetite, energy intake (EI), energy expenditure (EE), plasma levels of triglycerides (TAG), and free fatty acids (FFA) in humans. First, 20 healthy males received intravenous infusion of GIP (0.8 pmol·kg−1·min−1) or saline for 300 min during and after a fixed meal ( protocol 1). GE was measured using paracetamol, appetite sensations using visual analog scales, EE using indirect calorimetry, and EI during a subsequent ad libitum meal (at 300 min). Next, 10 healthy males received intravenous infusions of Intralipid, glucose, or Intralipid plus glucose, with and without GIP (1.5 pmol·kg−1·min−1) for 300 min ( protocol 2). In protocol 1, GIP did not have any effect on GE, EI, EE, removal of TAG, or FFA and did not influence the subjective feeling of hunger, satiety, fullness or prospective food consumption compared with saline. In protocol 2, no difference was seen ...
The American Journal of Clinical Nutrition, 2009